Dissertations / Theses: 'CD11'

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Johansson, Joakim, Florence Sjögren, Mikael Bodelsson, and Folke Sjöberg. "Dynamics of leukocyte receptors after severe burns: An exploratory study." Linköpings universitet, Hälsouniversitetet, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-67169.

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Background: Patients with burns are susceptible to organ failure, and there is indirect evidence that leukocytes may contribute to this process. They may change the expression of cell-surface receptors after certain stimuli, for example, the burn. We therefore aimed to assess the changes induced by the burn in the expression of leukocyte cell-surface receptors CD11b, CD14, CD16, and CD62L on the surface of PMNs and monocytes. We also wanted to examine the dynamics of this activation during the first week after the burn, and to relate it to the size of the injury. Methods: Ten patients with burns of andgt;15% (TBSA) were included in the study. Blood samples were collected on arrival and every consecutive morning during the first week. Healthy volunteers acted as controls. Results: PMN CD11b expression was increased. The extent of PMN CD11b expression correlated negatively to the size of the full thickness burn. Monocyte CD14 expression increased initially but there was no relation to the size of the burn. PMN CD16 expression decreased initially during the first days and the decrease was related to burn size. CD62L did not vary depending on the burn in either PMN or monocytes during the first week after the burn. Conclusion: This study showed that specific receptors on the surface of leukocytes (PMN CD11b, monocyte CD14 and PMN CD16) are affected by the burn. Expression of PMN CD11b and CD16 are related to burn size. Burn-induced effects on the expression of PMN receptors, such as PMN CD11b and CD16, may contribute to burn-induced infection susceptibility.
Original Publication: Joakim Johansson, Florence Sjögren, Mikael Bodelsson and Folke Sjöberg, Dynamics of leukocyte receptors after severe burns: An exploratory study, 2011, BURNS, (37), 2, 227-233. http://dx.doi.org/10.1016/j.burns.2010.08.015 Copyright: Elsevier Science B.V., Amsterdam. http://www.elsevier.com/

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Daniels, Brodie Belinda. "Molecular and cellular analysis of the interaction between soluble CD23 and CD11/CD18 integrins." Thesis, Nelson Mandela Metropolitan University, 2010. http://hdl.handle.net/10948/1217.

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The low affinity IgE receptor, CD23, is expressed by a wide variety of cells and cleaved from its original 45 kDa size to several smaller soluble CD23 proteins. Soluble CD23 function depends on the form of the protein and its interaction with various ligands. CD23 is believed to play an important role in regulating allergic responses and in inflammation, amongst others. β2 integrins are important in a variety of cell-adhesion reactions during immune-inflammatory mechanisms and the binding of their natural ligands generates outside-in cellular signalling, leading to cell activation. Although the binding of CD23 to β2 integrins contributes to this signalling in monocytes, the interaction site for CD23 is unknown. This study focused on the interaction of three soluble CD23 proteins with the β2 integrins CD11b/CD18 and CD11c/CD18. Differentiated HL60, THP1 and U937 monocytic cells were used to demonstrate the binding of three recombinant CD23 constructs (corresponding to 16, 25 and 33 kDa human soluble CD23) to upregulated CD11b/CD18 and CD11c/CD18. This binding was partially blocked by an antibody specific for the CD11b/CD18 αI domain, demonstrating that αI domains are involved in binding to CD23. Recombinant αI domain proteins of CD11b and CD11c were demonstrated to bind CD23 using ELISA and in surface plasmon resonance spectroscopy. The dissociation constants for CD23-CD11b/CD18 and CD23-CD11c/CD18 are comparable to other integrin ligands. This study has shown that CD23 interacts directly with the αI domains of β2 integrins and that the interaction surface likely spans the lectin domain as well as either the stalk and/or C-terminal tail of CD23. This study also looked at the effect that soluble CD23 proteins had on monocyte biology. It appears that iv sCD23 proteins have little effect on the phagocytic or chemotactic ability of monocytes, while an increase in oxidative burst was shown with the 16 kDa and 25 kDa CD23 proteins. Signalling pathways for the production of reactive oxygen species were investigated and it appears that the CD23 proteins signal mainly through the phosphoinositide-3 kinase pathway, although the mitogen activated protein kinase and Src kinase pathways may also play a role. These data suggest that sCD23 proteins induce outside-in signalling of β2 integrins and are able to change the activation state of CD11b/CD11c by stimulating oxidative burst. This needs to be further investigated by determining how the three sCD23 proteins are binding the CD11 proteins and investigating further leukocyte function and inflammatory responses by the cells.

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Fagerholm, Susanna. "Bidirectional signalling and phosphorylation of CD11 /." Helsinki : University of Helsinki, 2002. http://ethesis.helsinki.fi/julkaisut/mat/bioti/vk/fagerholm/.

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Faulhaber, Fabrízia Rennó Sodero. "Expressão de marcadores de superfície de neutrófilos em recém nascidos ictéricos antes e após a fototerapia." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2017. http://hdl.handle.net/10183/179819.

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A icterícia por hiperbilirrubinemia indireta afeta mais de 60% dos recém-nascidos a termo. O tratamento, quando necessário, é realizado através da fototerapia. Não existem estudos na literatura avaliando os efeitos da fototerapia na função dos neutrófilos de recém-nascidos. O melhor entendimento da função dos neutrófilos nos recém-nascidos antes e após a fototerapia seria importante para avaliar as possíveis repercussões na expressão dos neutrófilos desencadeadas pelo tratamento fototerápico. O objetivo deste estudo foi avaliar e comparar a função dos neutrófilos, através da mensuração pela citometria de fluxo da expressão dos principais marcadores de superfície em recémnascidos ictéricos, antes e após 24 horas de fototerapia. Metodologia: Foram incluídos recém-nascidos com idade gestacional ≥ 35 semanas e peso de nascimento ≥ 2000g, que possuiam critérios da Academia Americana de Pediatria para tratamento fototerápico. Os critérios de exclusão foram: mal-formações congênitas, síndromes com alterações cromossômicas, erro inato do metabolismo, infecções do grupo STORCH, asfixia neonatal, sepse ou suspeita de sepse, exsanguineotransfusão, transfusão de hemocomponentes e uso de imunoglobulina. Foi realizada a avaliação de expressão da intensidade média de fluorescência (IMF) de CD10, CD11b, CD11c, CD15, CD16, CD18, CD62L, CD64 e CD66, antes do início e após 24 horas do início da fototerapia. Foram utilizados o teste T de Student para análise dos dados. Resultados: Foram incluídos 25 recém-nascidos no estudo, com idade mediana de 53 (27.5-75.5) horas de vida e bilirrubina média de 13.6±2.85 mg/dL. Não houve diferença estatística na expressão de CD11b, CD15, CD18, CD62L, CD64 e percentual de neutrófilos antes e após 24 horas de fototerapia. Ocorreu aumento da expressão de CD10 8 (p=0.038) e CD16 (p=0.017) e redução da expressão de CD11c (p=0.023) e CD66acde (p=0.004) após 24 horas de fototerapia. Conclusão: Os recém-nascidos submetidos ao tratamento fototerápico apresentaram aumento da expressão de CD10 e de CD16 e diminuição da expressão de CD11c e de CD66acde após 24 horas de exposição, que pode estar relacionado a um efeito antiinflamatório da fototerapia nos recém-nascidos expostos a este tratamento.
Jaundice due to indirect hyperbilirubinemia affects more than 60% of term neonates. The treatment when necessary is carried out using phototherapy. There are no studies in the literature evaluating the effect of phototherapy on the function of neonates' neutrophils. A better understanding of the function of neutrophils in neonates before and after phototherapy would be important in order to assess potential effects on the expression of neutrofils triggered by the phototherapy treatment. The aim of this study was to assess and compare the function of neutrophils by measuring the expression of the main surface markers in icteric neonates, using flow cytometry, before and after 24 hours of phototherapy. Methodology: Neonates at a gestational age ≥ 35 weeks and at a birth weight ≥ 2000g who met the criteria of the American Academy of Pediatrics for phototherapy were included. The exclusion criteria were: congenital malformations, syndromes with chromosomal alterations, inborn errors of metabolism, infections of the STORCH group, neonatal asphyxia, sepsis or suspicion of sepsis, exchange transfusion, transfusion of blood components, and use of immunoglobulin. The evaluation of the MFI expression of CD10, CD11b, CD11c, CD15, CD16, CD18, CD62L, CD64 and CD66 was performed before and 24 hours after the initiation of phototherapy. The chi-square and Student T tests were used for data analysis. Results: Twenty-five neonates were included in the study at the mean age of 53 (27.5- 75.5) hours of life and with a mean bilirubin level of 13.6±2.85 mg/dL. There was no statistical difference in the expression of CD11b, CD15, CD18, CD62L, CD64 and percentage of neutrophils before and after 24 hours of phototherapy. There was an increase in the expression of CD10 (p=0.038) and CD16 (p=0.017) and a reduction in 10 the expression of CD11c (p=0.023) and CD66acde (p=0.004) after 24 hours of phototherapy. Conclusion: The newborns submitted to phototherapy had increased expression of CD10 and CD16 and decreased expression of CD11c and CD66acde after 24 hours of exposure, which may be related to an anti-inflammatory effect of phototherapy on the neonates exposed to this treatment.

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Owen, Caroline Ann. "Monocyte adherence to fibronectin : role of CD11/CD18 integrins and relationship to other monocyte functions." Thesis, University of Birmingham, 1993. http://etheses.bham.ac.uk//id/eprint/36/.

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Regulated adherence of monocytes to extracellular matrix macromolecules is a prerequisite for their accumulation at sites of pulmonary infection and inflammation. To begin to assess the pathobiological importance of alterations in monocyte adherence to extracellular matrix in inflammatory lung diseases, the adherence properties of monocytes from patients with an inflammatory lung disease (bronchiectasis) and healthy subjects to a representative matrix component (fibronectin) were compared. Spontaneous adherence of monocytes from the control subjects was 20 to 25%, whereas that of the patients' cells was 2 to 3-fold higher and correlated with the severity of airway inflammation. Endotoxin (LPS) and cytokines from areas of airway disease are likely to be responsible for the observed monocyte activation since: 1) LPS was detected in plasma from all of the patients but none of the control subjects; and 2) LPS and cytokines produced dose-related increases in the adherence of normal monocytes in vitro. Monocyte adherence to fibronectin was substantially mediated by CD11/CD18 integrins, via both RGD-dependent and RGD-independent mechanisms. These data indicate that signals arising from foci of pulmonary inflammation are likely determinants of the accumulation of monocytes in the lungs of patients with chronic inflammatory lung diseases. There was a striking relationship between the adherence properties of monocytes and functions that are of biological importance at sites of inflammation. Spontaneously adherent monocytes had an "inflammatory effector" phenotype, non-adherent cells had an "immune modulatory" phenotype and monocytes that could stimulated to adhere by LPS (LPS-adherent cells) had an intermediate phenotype. In addition, only the adherent monocyte subpopulations were replete with HLE and these cells contained a substantial (10 to 11-fold) molar excess of HLE compared with the physiological inhibitor of this enzyme (a1-antitrypsin). Maturation in vitro increased the accumulation of a1-antitrypsin by all of the monocyte subpopulations. In contrast, proinflammatory mediators up-regulated a1-antitrypsin accumulation by only the spontaneously adherent cells, probably by translational or post-translational mechanisms. In conclusion, these data indicate that monocytes are heterogeneous in their ability to accumulate at sites of infection and inflammation. In addition, the capacity of monocytes to adhere to fibronectin is related to monocyte functions that are of biological importance at sites of infection and inflammation. Furthermore, LPS released from foci of infection, may induce the accumulation of monocytes with an inflammatory effector phenotype, and may thereby promote resolution of tissue infection. Alternatively, LPS may promote the recruitment of monocytes with capacity to contribute to HLE-mediated tissue injury.

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Baj, Agnes [Verfasser]. "Polymorphismen im CD11-Cluster bei Patienten mit Koronarer Herzerkrankung / Agnes Baj." Kiel : Universitätsbibliothek Kiel, 2011. http://d-nb.info/1020202610/34.

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Sloma, Ivan. "Biologie des protéines CD1a, CD1b et CD1c : De l'expression monocytaire à la présentation de l'antigène par les cellules dendritiques." Paris 5, 2007. http://www.theses.fr/2007PA05D036.

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Les protéines CD1a, CD1b et CD1c sont des molécules non classiques de présentation de l'antigène. Leur structure est analogue à celle des protéines du complexe majeur d'histocompatibilité de classe I. Exprimées par les cellules dendritiques, elles présentent des antigènes lipidiques à des lymphocytes T spécifiques qui vont participer aux réponses immunes anti-infectieuses et anti-tumorales. Après un rappel de l'état des connaissances sur les protéines CD1 du groupe I et les cellules dendritiques, ce manuscrit présente tout d'abord les résultats de trois études s'intéressant à l'expression monocytaire des protéines CD1 dans la drépanocytose et sa relation avec la susceptibilité aux infections bactériennes. Dans un deuxième temps sont développées les études de l'organisation membranaire de la protéine CD1a, son impact sur l'activation lymphocytaire T et l'implication de CD1a dans l'induction d'un signal de maturation de la cellule dendritique
CD1a, CD1b and CD1c proteins are non classical MHC-class I antigen presenting molecules. They display structural homology with MHC-class I proteins. Expressed on dendritic cells, they present glycolipid antigens to specific T lymphocytes with participate to anti-infectious and anti-tumoral immune responses. After an extensive review on CD1 antigen presenting system and dendritic cell populations, this manuscript presents firstly three studies on CD1 expression on monocytes in sickle cell disease and its relation with susceptibility towards severe bacterial infection. In a second part data on CD1a membrane organization and its impact on T cell activation and dendritic cell maturation are presented

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Welcker, Silvia. "Selektion konformationsspezifischer Aptamere sowohl gegen das aktivierte Leukozytenintegrin Mac-1 (alphaM beta 2, CD11b, CD18) als auch gegen den nicht aktivierten und aktivierten Integrin-Rezeptor alphaV Beta 3 (Vitronektin-Rezeptor, CD51,CD61)." [S.l. : s.n.], 2007. http://nbn-resolving.de/urn:nbn:de:bsz:25-opus-44251.

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Pyszniak, Andrew M. "Regulation of LFA-1 (CD11a/CD18) function." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq25139.pdf.

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Wohler, Jillian E. "The role of the [beta]₂-integrin family on T cell subsets." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2009. https://www.mhsl.uab.edu/dt/2009p/wohler.pdf.

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Osmers, Inga. "Reduzierte Expression der Membranrezeptoren CD14 und CD11b auf Leukozyten Frühgeborener." [S.l.] : [s.n.], 2004. http://www.diss.fu-berlin.de/2004/256/index.html.

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Joeinig, Anke. "Die Rolle der CD14+CD16+ Monozyten in der autologen peripheren Stammzelltransplantation." Diss., kostenfrei, 2008. http://edoc.ub.uni-muenchen.de/9157/.

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Hollenbach, Marcus. "Die immunmodulatorische Wirkung von Ethylpyruvat." Doctoral thesis, Universitätsbibliothek Leipzig, 2011. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-78494.

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In einer Vielzahl von Arbeiten konnten anti-inflammatorische Eigenschaften von Ethylpyruvat (EP) aufgezeigt werden. An verschiedenen Modellen der Sepsis, des hämorrhagischen Schocks, von Verbrennungsschäden, des Apoplex oder der Ischämie und Reperfusion wurde bei der Behandlung mit EP ein protektiver Effekt sowie eine verminderte Produktion von pro-inflammatorischen Zytokinen nachgewiesen. Als biochemische Grundlage wurde die Interaktion von EP mit dem Transkriptionsfaktor NF-κB identifiziert, die spezifischen Regulationsmechanismen konnten bisher allerdings nicht zufriedenstellend aufgeklärt werden. In dieser Arbeit wurde als eine neue mögliche Erklärung für die anti-inflammatorischen Eigenschaften des EP und weiterer α-oxo-Karbonsäureester die Inhibierung der Glyoxalase I (Glo-I) aufgezeigt. In vitro-Experimente zur Enzymaktivität belegten die Hemmung der Glo-I durch EP, während α-Hydroxy-Karbonsäureester wie L-Ethyllaktat (EL) keine inhibierenden Eigenschaften aufwiesen. Dennoch waren sowohl EP als auch EL und weitere Laktatester in der Lage, die LPS-induzierte Produktion von pro-inflammatorischen Zytokinen wie IL-1β, IL-6, IL-8 und TNF-α von humanen immunkompetenten Zellen zu supprimieren und die Expression von Immunrezeptoren wie HLA-DR, CD14 und CD91 zu modulieren. Somit konnten erstmals anti-inflammatorische Eigenschaften von Laktatestern nachgewiesen sowie eine Verbindung zwischen den Glyoxalase-Enzymen und dem Immunsystem etabliert werden. Diese und weitere Ergebnisse zur Einflussnahme der Karbonsäureester auf die Zellvitalität präsentieren das Glyoxalasesystem als mögliches Ziel neuer Therapiekonzepte für die Immunsuppression und bestätigen dessen Bedeutung für die Entwicklung von Anti-Tumor-Agenzien.

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Del, Nagro Christopher J. "B cell co-receptors CD19 and CD21 in tolerance and auto-immunity." Diss., Connected to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2005. http://wwwlib.umi.com/cr/ucsd/fullcit?p3190009.

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Thesis (Ph. D.)--University of California, San Diego, 2005.
Title from first page of PDF file (viewed March 14, 2006). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.

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Weitzman, Jonathan B. "Characterisation of the 5' regions of the leukocyte integrin CD11b/CD18 genes." Thesis, University of Oxford, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.292365.

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Toschka, Robert. "Identification of human peripheral blood monocyte derived pro-inflammatory dendritic cells." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2014. http://dx.doi.org/10.18452/17040.

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Dendritische Zellen (DZ) sind essentiell für die Aktivierung von Immunantworten. Drei Flt3-abhängige DZ Populationen aus dem Blut bestehend aus konventionellen (kDZ) BDCA1+ DZs und BDCA3+ DZs und plasmazytoide DZs wurden bereits beschrieben. Hier wurden zum ersten Mal sich aus Monozyten entwickelnde DZ (moDZ), genauer BDCA1+CD14+ pro-inflammatorische DZ (pro-iDZ) aus periphärem Blut unter homöostatischen Bedingungen identifiziert. Isolierte pro-iDZ sekretierten spontan große Mengen an pro-inflammatorischen Zytokinen, die kDZ reifen ließen und T Zell Proliferation unterstützten. Sie waren BDCA1+CD14- DZ und CD14+CD16- Monozyten in der TH17 Zell Induktion überlegen. Pro-iDZ ähnliche BDCA1+CD14+ Zellen konnten durch imaging cycler microscopy in Geweben von Patienten die an Psoriasis, Dermatomyositis oder entzündetem Halonävus erkrankt waren identifiziert werden. Ihr Fehlen in gesunder Haut deutete eine Rekrutierung von pro-iDZs in entzündetes Gewebe an. Eine Verwandtschaftsanalyse von pro-iDZ zwischen Monozyten, kDZ des Blutes und in vitro generierten moDZ auf genomweiter Ebene wies auf einen monozytären Ursprung hin. Anylse mittels funktioneller Annotation auf differentiell exprimierten Genen zwischen pro-iDZ und Monozyten zeigte eine DZ spezifische Gensignatur auf. Diese Gene waren insgesamt in der gleichen Weise wie in kDZ und moDZ reguliert, das eine Entwicklung von Monozyten nach DZ nahelegte. Dieses Entwicklungskonzept wurde insofern unterstützt, indem unter entzündlichen Bedingungen kultivierte CD14+CD16- Monozyten BDCA1 Expression und DZ Funktion erlangten. Da pro-iDZ sehr ähnlich zu BDCA1+CD14+ Zellen aus entzündeter Haut waren und beide große Konvergenz mit zuvor beschriebenen BDCA1+CD14+ inflammatorischen DZ (infDZ) aus entzündeten Geweben aufwiesen, können pro-iDZ als direkte infDZ Vorläufer angesehen werden. Dadurch und wegen ihrer monozytären Herkunft können pro-iDZ als Beweis für die humane Differenzierung von Monozyten nach DZ in vivo betrachtet werden.
Dendritic cells (DCs) are critical for the activation of immune responses. Three Flt3-dependent blood DC populations including conventional BDCA1+ DCs and BDCA3+ DCs (cDCs) and plasmacytoid DCs were described previously. This work identifies for the first time human peripheral blood monocyte derived BDCA1+CD14+ pro-inflammatory DCs (pro-iDCs) during steady state. Isolated pro-iDCs spontaneously secreted high amounts of pro-inflammatory cytokines, which matured cDCs and promoted T cell proliferation. They were superior in priming TH17 cells when compared to BDCA1+CD14- DCs and CD14+CD16- monocytes. BDCA1+CD14+ cells resembling blood pro-iDCs as identified by imaging cycler microscopy were found in samples from patients suffering from psoriasis, dermatomyositosis and inflamed halo nevus. Their absence in healthy donor’s skin indicated a recruitment of pro-iDCs to sites of inflammation. Analysis of the developmental relationship of pro-iDCs between monocytes, blood cDCs and in vitro generated monocyte derived DCs (moDCs) on whole genome level strongly suggested a monocytic origin. Functional annotation analysis of differentially regulated genes between monocytes and pro-iDCs revealed a DC specific gene signature. In addition, these genes were overall regulated in the same way in blood cDCs and moDCs, indicating an ongoing development of pro-iDCs from monocytes towards DCs. This developmental concept was supported as CD14+CD16- monocytes cultured under inflammatory conditions gained BDCA1 expression and DC function. Since pro-iDCs were highly similar to BDCA1+CD14+ cells found in inflamed skin and as both showed a marked convergence with BDCA1+CD14+ inflammatory DCs (infDCs) present in inflamed tissues described previously, pro-iDCs can be regarded as immediate precursors of infDCs. Thus, in respect of a monocytic origin and a presumably inflammatory DC fate, pro-iDCs may constitute a missing link to prove human moDC differentiation in vivo.

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Blumenthal, Antje [Verfasser]. "Charakterisierung der Tetraspanine CD9, CD81 und CD151 in einer permanenten murinen Podozytenzelllinie / Antje Blumenthal." Greifswald : Universitätsbibliothek Greifswald, 2012. http://d-nb.info/1024147320/34.

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Brunialti, Milena Karina Coló [UNIFESP]. "Expressão de TLR2, TLR4, CD14, CD11b e CD11c na superfície de monócitos e resposta in vitro ao LPS, avaliada pela produção de citocinas, em pacientes com sepse grave e choque séptico." Universidade Federal de São Paulo (UNIFESP), 2005. http://repositorio.unifesp.br/handle/11600/20859.

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A sepse apresenta crescente incidência e elevada morbidade e mortalidade, sendo a principal causa de óbito nas unidades de terapia intensiva. O controle da infecção depende do adequado reconhecimento dos microrganismos pelas células do hospedeiro e de resposta efetora competente. Paradoxalmente, na sepse, os mecanismos de proteção estão também envolvidos no processo de doença, sendo o limite entre resposta protetora e de lesão ainda impreciso. Objetivos: Avaliar a expressão de receptores de reconhecimento de patógenos na superfície de monócitos e a resposta a estímulos exógenos - LPS, IL-1 P e TNF-α - in vitro, medida pela produção de citocinas, em pacientes em diferentes estádios da sepse. Métodos: Foram incluídos 41 pacientes, classificados de acordo com as definições do consenso de 1992 sendo, 14 com sepse, 12 com sepse grave e 15 com choque séptico. Dezessete voluntários sadios foram incluídos como controle. Através da citometria de fluxo, a expressão de TLR2, TLR4, CD14, CD11b e CD11c foi analisada na superfície dos monócitos em sangue total. A forma solúvel do receptor CD14 (sCD14) também foi mensurada em soro através de ELlSA. A produção de citocinas inflamatórias (TNF-α e IL-6) e antiinflamatória (IL-10) foi mensurada em sobrenadante de células mononucleares do sangue periférico após os estímulos de LPS, IL-1 P e TNF-α in vitro. Resultados: Foi detectado aumento do sCD14 sérico e uma queda expressão de mCD14 em monócitos periféricos nos pacientes em relação aos voluntários sadios (p<0,01). Entretanto não houve diferença entre os grupos estudados quanto à expressão dos receptores TLR2, TLR4, CD11b e CD11c. O grupo com sepse apresentou, comparado com os outros grupos, aumento da produção de IL-6 e TNF-α após o estímulo de LPS. Esta regulação positiva foi menos intensa com IL-1 p e ausente com TNF-α Uma regulação negativa da produção de citocinas inflamatórias foi observada na sepse grave e choque séptico. Não foi observada diferença significante na produção de IL-10 entre os grupos, todavia uma menor produção frente ao estímulo de LPS foi detectada nos pacientes em choque séptico em relação aos pacientes em sepse (p<0,05). A correlação entre receptores de superfície de monócitos e produção das citocinas frente ao LPS pode ser demonstrada quando os resultados obtidos dos pacientes sépticos foram agrupados. Surpreendentemente, detectou-se correlação da expressão dos mesmos receptores com os outros estímulos utilizados, IL-1 p e TNF-α., também foi observada. Conclusões: Neste estudo demonstramos que a resposta inflamatória está associada com o continuum de manifestações clinicas, com uma forte resposta na fase inicial (sepse) e quadro refratário nas fases tardias (sepse grave e choque séptico). A correlação observada entre os receptores de superfície e a produção de citocinas frente aos estímulos de TNF-α e IL-1p e o mesmo padrão de resposta observado com os diferentes estímulos sugere um padrão de resposta imunológica que não depende apenas da expressão dos receptores avaliados e provavelmente, tem uma regulação na via de sinalização intracelular.
Sepsis presents increasing incidence and high morbidity and mortality and is the main cause of death in the intensive care units. The infection control depends on the adequate microorganism recognition by the host cells and competent effector’s response. Paradoxically, in sepsis, the protective mechanisms are also involved in the illness process, with the limit between protective and harmful response still inexact. Purpose: To evaluate the expression of pathogen recognition receptors on monocytes surface and the response to exogenous stimulus - LPS, IL-1β e TNF-α - in vitro, measured by the cytokine production, in patients in different sepsis stages. Methods: Forty one patients, classified in accordance with the definitions of the Consensus of the 1992, had been enrolled: 14 with sepsis, 12 with severe sepsis and 15 with septic shock. Seventeen healthy volunteers were included as control. Through flow cytometry, the expression of TLR2, TLR4, CD14, CD11b and CD11c were analyzed on monocytes surface in whole blood. The soluble form of CD14 receptor (sCD14) also was measured in serum by ELISA. Inflammatory (TNF-α and IL-6) and anti-inflammatory (IL-10) cytokine levels was measured in peripheral blood mononuclear cells supernatants following LPS, IL-1β e TNF -α - stimulus in vitro. Results: An increase in sCD14 in sera and a decreased mCD14 expression on peripheral monocytes were found in patients comparing to healthy volunteers (p<0,01). However, no differences in the expression of TLR2, TLR4, CD11b and CD11c were found among the groups. The sepsis group showed, compared with the others groups, higher IL-6 and TNF-α production after LPS stimulus. This positive regulation was less intense with IL-1β and absent with TNF- α. A negative regulation of the inflammatory cytokine production was observed in severe sepsis and shock septic patients comparing to the sepsis and healthy group, independent of the stimulus. No significant difference in the IL-10 production was found among the groups, yet a lower production after LPS challenge was detected in septic shock compared with the sepsis patients (p<0,05). A correlation between monocytes surface receptors and cytokine production after LPS challenge could be demonstrated when the results of the septic groups had been grouped. Surprising, correlation of the expression of the same receptors with the other stimulus used, IL-1β e TNF-α, were also observed. Conclusions: In this study we show that the inflammatory response is associated with the continuum of clinical manifestations of sepsis, with a strong inflammatory response in the early-phase (sepsis) and refractory picture in the late-phases (severe sepsis and septic shock). The correlation between the cell surface receptors and the cytokine production after IL-1β e TNF-α stimuli and the observation of one same standard response with the different stimulus suggest a pattern of immunology response that does not depend only of the expression of the evaluated receptors and, probably, has a regulation in the intracellular signaling pathways.
BV UNIFESP: Teses e dissertações

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Gesenberg, Jan [Verfasser]. "CD11b/CD18 Knock-Out reduziert die Anfälligkeit für ventrikuläre Tachykardie und die Infarktgröße / Jan Gesenberg." Köln : Deutsche Zentralbibliothek für Medizin, 2018. http://d-nb.info/1153425432/34.

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Azevedo, Isaclaudia Gomes de. "Caracterização do papel da integrina CD11d/CD18 na injúria pulmonar aguda durante a malária experimental." Instituto Oswaldo Cruz, 2012. https://www.arca.fiocruz.br/handle/icict/6940.

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Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil
A malária é uma doença parasitária causada pelo protozoário do gênero Plasmodium e é um grande problema de saúde pública. Por volta de 40% da população mundial está em área de risco de malária. A malária cerebral é a principal complicação, mas o edema pulmonar e a injúria pulmonar (ARDS) podem ser desencadeadas pela infecção com P. falciparum, P. vivax e P. knowlesi, e ocorrem frequentemente durante ou após o início do tratamento antimalárico. Os mecanismos moleculares e celulares de indução de injúria pulmonar, como da malária cerebral permanecem indefinidos. Previamente, nós encontramos que a deleção genética da integrina CD11d/CD18, que é expressa em leucócitos mieloides, desencadeia uma maior sobrevida no animais infectados com Plasmodium berghei Anka (PbA), que é uma modelo de malária grave. Tal resultado sugere que a molécula CD11d/CD18 tenha um papel determinante na imunopatogênese da malária. Perguntamos se CD11d/CD18 determina eventos fisiopatológicos na ARDS desencadeadas por infecção PbA. Realizamos análises da expressão da subunidade CD11d e de parâmetros inflamatórios, como da permeabilidade da barreira vascular por exclusão do corante azul de Evans, e citocinas por ELISA. Proteínas e leucócitos foram mensurados no lavado broncoalveolar (LAB). A migração celular foi medida pela contagem de células ao microscópio e por citometria de fluxo. Também foi avaliada a expressão do ligante de CD11d, VCAM-1 e a função respiratória dos animais. A Análise da expressão do mRNA da subunidade CD11d sugere um acúmulo de leucócitos e/ou que a expressão da subunidade CD11d é aumentada em macrófagos pulmonares e/ou em outras células mieloides pulmonares após a infecção. Nós também observamos um acumulo de leucócitos, hemácias e fluido nos pulmões de CD11d+/+ mice. A inflamação e a hemorragia foram menos intensas nos pulmões dos animais CD11d-/-. Em paralelo, a integridade da barreira vascular foi prejudicada nos animais CD11d+/+, enquanto os animais CD11d-/- tinham menor extravazamento de azul de Evans no tecido pulmonar e níveis mais baixos de proteína no LAB em comparação com CD11d+/+, apesar de o número total de leucócitos no LBA ter sido semelhante. Observamos níveis mais baixos de citocinas inflamatórias que estavam associadas com a malária experimental e clínica, em amostras de animais CD11d-/- quando comparados com os animais CD11d+/+. A maior parte dos leucócitos dos camundongos CD11d-/- ficavam retidos na medula óssea e também havia menos células CD14+ no sangue periférico, quando comparado com os camundongos CD11d+/+. Os nossos resultados demonstram que a ausência da subunidade CD11d não interfere na expressão de VCAM-I e acarreta uma melhor função respiratória após a infecção. Podemos observar que a integrina CD11d/CD18 influência nos principais eventos fisiopatológicos na ARDS desencadeada pela malária experimental, incluindo ruptura da barreira vascular pulmonar, inflamação e hemorragia.
Malaria is a parasitic disease caused by protozoa of the genus Plasmodium and is a major public health problem. 40% or more of the global population is at risk for malaria. Cerebral malaria is the most feared complication, but pulmonary edema and lung injury (ARDS) are also triggered by the infection with Plasmodium falciparum, Plasmodium vivax, and Plasmodium knowlesi, and often occur during or after the begin of anti-malarial therapy. The molecular and cellular mechanisms of pulmonary injury, like those of CM, remain incompletely defined. Previously, we found that genetic deletion of integrin CD11d/CD18, which is expressed on myeloid leukocytes, improves survival in mice infected with P. berghei Anka (PbA), a model of severe malarial infection. Thus, CD11d/CD18 may be a critical determinant in injurious innate immune responses to malarial parasites. We asked if CD11d/CD18 is involved in pathophysiologic events in ARDS triggered by PbA infection. We measured CD11d subunit expression, vascular barrier function by Evans blue dye (EBD) exclusion, and cytokines by ELISA. Protein and leukocytes were measured in bronchoalveolar lavage (BAL) samples. Cell migration was measured by microscope counting and flow cytometry. We also analyzed the expression of the ligand to CD11d, VCAM-1, and respiratory function of animals. Analysis of CD11d mRNA suggested that CD11d subunit expressing leukocytes accumulate and/or that CD11d subunit expression is increased in lung macrophages or other pulmonary myeloid cells early after infection. We showed a dramatic accumulation of leukocytes, red blood cells, and fluid in the lungs of CD11d+/+ mice. Inflammation and hemorrhage were reduced in the lungs of CD11d-/- animals. In parallel, vascular barrier integrity was impaired in CD11d+/+ animals; once CD11d-/- animals had less accumulation of EBD in extravascular lung tissue and lower levels of BAL protein compared to CD11d+/+, although the total number of BAL leukocytes was similar. Compared to CD11d+/+, there were lower levels of inflammatory cytokines that are associated with experimental and clinical malaria in samples from CD11d-/- mice. Most of the leukocytes in CD11d-/- mice are retained in the bone marrow and also there is less CD14+ in the peripheral blood when compared to CD11d+/+ mice. Our findings demonstrate that the absence of CD11d integrin does not interfere in VCAM-I expression and correlates with a better respiratory function in infected CD11d-/- when compared to CD11d+/+ mice. We observed that CD11d/CD18 influences key pathophysiologic events in ARDS in experimental malaria, including pulmonary vascular barrier disruption, inflammation, and hemorrhage.

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BLOUIN, ERIC. "Etude des mecanismes de regulation de l'activation des integrines 2 cd11b/cd18 des polynucleaires neutrophiles." Paris 6, 2001. http://www.theses.fr/2001PA066271.

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Les neutrophiles sont les premiers leucocytes a acceder au site inflammatoire. C'est l'adherence, via les integrines 2, qui leur permet d'assurer leurs fonctions. Les mecanismes d'activation de ces integrines sont mal connus. Cette etude analyse donc le role de l'oxydoreduction dans l'activation des integrines 2 des neutrophiles. Nous montrons que les oxydants activent les integrines 2, se traduisant par l'adherence des neutrophiles et l'apparition de la conformation active des integrines. Cette activation implique les tyrosine kinases et la formation de ponts disulfure. Ensuite, le dpi (diphenyleneiodonium) et les piegeurs de radicaux libres inhibent l'adherence et l'apparition de la conformation active des integrines 2, induite apres la stimulation des neutrophiles par le tnf-. L'oxydase impliquee dans le mecanisme n'est pas la nadph-oxydase, puisque les memes resultats sont retrouves avec les neutrophiles de patients cgd (granulomatose septique chronique). Le pp2, inhibiteur specifique des kinases src, bloque l'adherence des neutrophiles et l'apparition de la conformation active des integrines 2 induite par le tnf-. Parmi les kinases src, seules les kinases fgr sont activees par le tnf- et ceci de facon dependante de l'oxydoreduction, car inhibee par le dpi et les piegeurs de radicaux libres. De la meme facon, le sb203580, inhibiteur specifique des map kinases p38, bloque l'adherence des neutrophiles et l'apparition de la conformation active des integrines 2 induite par le tnf-. Cette activation est regulee de facon dependante de l'oxydoreduction, car elle est bloquee par le dpi et les piegeurs de radicaux libres. Nous avons donc mis en evidence un nouveau mecanisme de regulation de l'activation des integrines 2, impliquant la stimulation d'une oxydase, differente de la nadph-oxydase, qui modifie le potentiel d'oxydoreduction du neutrophile, entrainant l'oxydation de groupements thiols et l'activation des kinases p38 et fgr.

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Rieu, Philippe. "Etude de l'integrine cd11b/cd18 : analyse moleculaire et role au cours de l'adherence des neutrophiles." Paris 7, 1997. http://www.theses.fr/1997PA077273.

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Pour defendre l'organisme face a une agression tissulaire, les polynucleaires neutrophiles adherent a l'endothelium, le traversent et migrent dans le tissu conjonctif jusqu'au site inflammatoire ou ils liberent leurs produits de secretions, phagocytent les particules cibles, puis meurent par apoptose. Ce sont les integrines leucocytaires (cd11a, b, c, d/cd18) qui assurent les fonctions adhesives des neutrophiles. Parmi ces integrines, nous avons montre avec une souris invalide en cd11b, que le recepteur cd11b/cd18 est l'adhesine majeure des neutrophiles qui intervient dans l'adherence de ces cellules aux surfaces proteiques, dans la phagocytose et l'explosion respiratoire, et de facon inattendue, dans l'apoptose de ces cellules. Nous n'avons pas retrouve de recepteur des autres familles d'integrines en dehors d'une faible quantite de l'heterodimere cd49f/cd29. Par ailleurs, nous avons montre que la leucosialine (cd43), une mucine anti-adhesive fortement exprimee par les neutrophiles, subissait un clivage proteolytique au cours de l'activation cellulaire, ce qui pourrait faciliter la liaison de cd11b/cd18 avec ses ligands. Pour comprendre cette derniere interaction, nous avons caracterise le domaine d'adherence de l'integrine cd11b/cd18. Il s'agit d'un domaine extracellulaire d'environ 200 acides amines (domaine a ou i) qui adopte une structure de type alpha/beta et qui contient un site de fixation pour cation divalent a sa surface appele midas, metal ion-dependent adhesion site. C'est au niveau de ce site que se lient l'antagoniste nif (neutrophil inhibitory factor) et l'opsonine ic3b, deux ligands de cd11b/cd18. Le changement de conformation qui survient lors de l'activation des integrines pourrait modifier la coordination du metal du domaine a et faciliter ainsi l'interaction de midas avec ses ligands. Si la reaction inflammatoire est vitale pour l'organisme, une reponse excessive peut aggraver le traumatisme initial. La connaissance du role et du mode d'action des integrines leucocytaires devrait aider a la conception de nouveaux anti-inflammatoires.

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Matos, Jesamar Correia. "AnÃlise comparativa em histograma da intensidade de fluorescÃncia de CD10 e CD19 em blastos leucÃmicos e hematogÃnias." Universidade Federal do CearÃ, 2005. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=4290.

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CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
HematogÃnias sÃo cÃlulas jovens normais da medula Ãssea responsÃveis pela produÃÃo das cÃlulas de linhagem B do sistema imunolÃgico. A leucemia linfoblÃstica aguda de cÃlulas precursoras B representa um dos tipos de transformaÃÃo neoplÃsica das hematogÃnias. Devido a alta similaridade do ponto de vista citolÃgico dos dois tipos celulares, Ã possÃvel haver erros de interpretaÃÃo na anÃlise citolÃgica, fazendo-se necessÃrio em algumas circunstÃncias o uso de tÃcnicas complementares diagnÃsticas para diferenciar as cÃlulas benignas das malignas. O uso de marcadores imunolÃgicos atravÃs de anticorpos monoclonais marcados com fluorescÃncia tem grande aplicabilidade nos laboratÃrios especializados como rotina no estudo das leucemias. Os antÃgenos CD10 e CD19 estÃo expressos em ambos os tipos celulares de forma que se faz necessÃria uma extensÃo no uso de outros marcadores para caracterizaÃÃo da natureza benigna ou maligna das cÃlulas. Testou-se possÃveis diferenÃas nas curvas de expressÃo de CD10 e CD19 dos dois tipos celulares. Foram colhidas 36 amostras de medula Ãssea de pacientes pediÃtricos nÃo neoplÃsicos como grupo controle. A idade variou de 24 dias de vida a 15 anos com uma mÃdia de 5 anos. Foram colhidas tambÃm 39 amostras de pacientes portadores de LLA de linhagem B por ocasiÃo do diagnÃstico. A idade variou de 4 meses a 14 anos com uma mÃdia de 6,6 anos. Analisou-se as diferenÃas nas distribuiÃÃes quanto a intensidade de fluorescÃncia pelas mÃdias, desvios-padrÃo, coeficientes de variaÃÃo, coeficientes de inclinaÃÃo e coeficiente de curtose para os dois marcadores CD10 e CD19 nos dois grupos. Os valores individuais de cada amostra foram comparados com os intervalos gerados pelos valores do grupo controle com os seguintes respectivos resultados de sensibilidade e especificidade: 89,7% e 75% para um cut-off de mÃdia+2DP; 79,5% e 100% para mÃdia+2,5DP; e 71,8% e 100% para mÃdia+3DP. ConclusÃo: A expressÃo de CD10 e CD19 em blastos e hematogÃnias Ã diferente podendo ser de utilidade prÃtica na distinÃÃo entre os dois tipos celulares.
Hematogones are normal immature cells from bone marrow that are responsible for the production of the immune systemâs B cell lineage. The acute lymphoblastic leukemia (ALL) of precursors B cells represents one type of neoplastic transformation of hematogones. Due to their high similarity there are risks of erroneous interpretation consequently making it necessary use to complementary diagnostic techniques. The CD10 and CD19 antigens are expressed on both types of cells so, it is necessary use other monoclonal antibodies to identify malign or benign nature. In attempt to avoid the use of different antibodies we investigate possible differences in the expression of CD10 and CD19 in both cell types. We collected 36 samples of bone marrow from non-neoplastic patients as a control group. The age raged from 0 to 15 years with an average of 5 years. It was also collected 39 samples from patients with ALL of B cells. The age ranged from 0 to 14 years with an average of 6.6 years. We analyzed the differences between the fluorescence intensity concerning average, standard deviation, variation, inclination and kurtosis coefficients for the two markers. The individual values of each sample were compared with the intervals generated by the values of the control group: MEÂ2SD; MEÂ2.5SD and MEÂ3SD. It was possible to distinguish the groups with 89.7% and 75%; 79.5% and 100% and 71.8% e 100% of sensibility and specificity, respectively for the intervals. In conclusion, the expression of CD10 and CD19 antigens on blasts and hematogones is significantly different and may be useful in the differentiation of both cell types

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Santos, Andressa Cristina Antunes. "Efeito da desnutrição proteica sobre aspectos da mobilização, migração e sinalização celular. Papel da glutamina na modulação desses processos." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/9/9136/tde-28042016-104055/.

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A desnutrição é uma condição nutricional que pode afetar muitos aspectos da resposta imunológica, como alterações na migração celular, na fagocitose, na resposta bactericida, mudanças na produção de radicais livres e espécies de nitrogênio e na produção de citocinas pró-inflamatórias. Logo, indivíduos desnutridos apresentam maior susceptibilidade a infecções. Visto que a glutamina é um aminoácido de extrema importância para a funcionalidade de diversas células do sistema imune e que as mesmas apresentam aumento da utilização desse aminoácido durante processos infecciosos, investigou-se, neste trabalho, quais os efeitos da glutamina sobre alguns aspectos da mobilização, migração e sinalização celular em um modelo experimental de desnutrição proteica. Para tanto, utilizou-se camundongos da linhagem BALB/c machos, os quais foram divididos em dois grupos, Controle e Desnutrido, que passaram a receber dietas isocalóricas contendo 12% (normoproteica) e 2% de caseína (hipoproteica), respectivamente, durante 5 semanas. Para as avaliações in vivo, animais de ambos os grupos receberam por via endovenosa 100µL de solução contendo 1,25µg de LPS e após 1 hora 0,75mg/Kg de L-glutamina (GLUT). Após o período de desnutrição ou de indução ao processo inflamatório, os animais foram eutanasiados e as amostras biológicas coletas. Foram avaliados nos animais estimulados in vivo hemograma, mielograma, as citocinas IL-10 e TNF-α circulantes e a expressão de CD11b/CD18 nos granulócitos do sangue periférico. Foi avaliado, in vitro, a capacidade migratória, a expressão de CD11b/CD18 de polimorfonucleados da medula óssea e do sangue periférico, bem como a síntese de citocinas IL-1α, IL-6, IL-10, IL-12 e TNF-α e a expressão de NF-κB e IκBα em células cultivadas em meio com 0; 0,6; 2 e 10 mM de GLUT. Os animais desnutridos apresentaram anemia, leucopenia, hipoplasia medular e diminuição na concentração sérica de proteínas, albumina e pré-albumina. A GLUT, in vitro, apresentou capacidade de reduzir a produção de IL-1α e IL-6, bem como a ativação da via do NF-κB. No modelo in vivo a GLUT, em animais estimulados com LPS, alterou a cinética de migração neutrofílica e reduziu a expressão de CD18, bem como diminuiu os níveis de TNFα circulantes.
Malnutrition is a nutritional condition that can affect many aspects of immune responses, affecting cell migration, phagocytosis, bactericidal response and changing free radicals production as nitrogen species and production of proinflammatory cytokines. Therefore, malnourished individuals are more susceptible to infections. Once glutamine is an amino acid of extreme importance to the functionality of various immune cells and those cells exhibit increased use of this amino acid during infectious processes. In this work was investigated, the effects of glutamine in some aspects of mobilization, cell migration and signaling in an experimental model of protein malnutrition. For this purpose, we used BALB/c mice, which received isocaloric diets, normoproteic or hypoproteic, containing respectively, 12% (Control group) and 2% (Malnourished group) of protein for a period of 5 weeks. The animals in both groups, for in vivo evaluations, received intravenous 100 µl of a solution containing 1.25µg of LPS and after 1 hour 0.75mg/kg of L-glutamine (GLUT). After the malnutrition period or the inflammatory process induction, the animals were euthanized and biological samples were collected. Were evaluated blood count, bone marrow, the cytokines IL-10 and TNF-α circulating and expression of CD11b/CD18 in granulocytes from peripheral blood of animals stimulated in vivo. In vitro were evaluated the migratory capacity, the expression of CD11b/CD18 polymorphonuclear bone marrow and peripheral blood, as well as the cytokines synthesis IL-1α, IL-6, IL-10, IL-12 and TNF-α and the expression of NF-κB and IκBα in cultured cells in media with 0; 0.6; 2 and 10 mM GLUT. Malnourished animals presented anemia, leukopenia, marrow hypoplasia and lower serum proteins, albumin and prealbumin. The GLUT in vitro has the capacity to reduce IL-1α and IL-6 as well as the activation of the NF-κB. In in vivo model, the GLUT altered neutrophil migration kinetics and reduced the expression of CD18, as well as decreased levels of circulating TNF-α in animals stimulated with LPS.

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Pereira, Melanie Claire. "The molecular analysis of the interation surface between sCD23 and the B2-integrins, CD11b & CD11c." Thesis, Nelson Mandela Metropolitan University, 2012. http://hdl.handle.net/10948/d1014734.

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Both CD23 and the β2 integrins (also known as CD11/CD18) have very important immunological functions, especially during the allergic response where the binding of CD23 to β2 integrins contributes to various types of signalling in monocytes which can result in drastic sensitivities experienced by some allergic individuals. CD23, also known as the low affinity receptor for immunoglobulin E or (FcεRII), is a type II transmembrane glycoprotein which is synthesized by haematopoietic cells and has biological activity in both membrane-bound and freely soluble forms. It acts via a number of receptors, including the β2 integrins. β2 integrins are specifically found on leukocytes and they play important roles in cell–cell or cell–matrix adhesion via their ability to bind multiple ligands. These molecules occur as heterodimers consisting of an alpha (α) and beta (β) subunit. The α-subunits of β2 integrins contain an approximately 200-amino-acid inserted domain or I-domain which is implicated in ligand binding function. There are four different types of β2 integrins, namely CD11a, CD11b, CD11c and CD11d, all dimers with the common beta subunit, CD18. CD23 and CD11/18 are natural ligands of each other; however the interaction site for CD23 is unknown. It is postulated that the integrin recognizes a tripeptide motif in a small disulfide-bonded loop at the N-terminus of the lectin head region of CD23, which is focussed around Arg172, Lys173 and Cys174 (RKC). This study thus focused on the interaction between the I-domain of CD11 (b and c) and a recombinant 25kDa construct of sCD23. In order to understand the characteristics of ligand binding between the relevant proteins of interest, alanine substitutions on the RKC motif of CD23 were made via site-directed mutagenesis. Consequently, a recombinant form of the I-domain of CD11 (b and c) as well as a wild type (containing the RKC motif) and mutant form (containing an AAC motif) of sCD23 were expressed and purified. The CD11 recombinant proteins were purified via affinity chromatography and the CD23 recombinant proteins via gel filtration chromatography. In addition, synthetic (CD23 derived) peptides, one containing the RKC sequence and the other the AAC sequence, were designed and custom synthesized. The synthetic peptides as well as the recombinant CD23 proteins were then analyzed for their interaction with the CD11 I-domain via ELISA. Subsequent ELISA analyses showed that the native sCD23 and the RKC peptide were able to bind to the integrin α I-domain whereas the mutant sCD23 and the corresponding synthetic AAC peptide failed to bind. This interaction was also analysed via flow cytometry using differentiated U937 cells, yielding similar results. ELISA analyses for the sCD23-CD11b I-domain interaction showed a Kd of 0.36 ± 0.14 μM whereas the RKC-CD11b I-domain interaction yielded a Kd of 1.75 ± 0.58 μM. Similarly, the sCD23-CD11c I-domain interaction yielded a Kd of 0.39 ± 0.09 μM and 1.53 ± 0.72 μM for the RKC-CD11c I-domain interaction. Peptide inhibitory analysis, analysed via ELISA and flow cytometry, reinforced the fact that the RKC motif on sCD23 is a prerequisite for ligand binding of the CD11b/c I-domain.

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Matos, Jesamar Correia. "Análise comparativa em histograma da intensidade de fluorescência de CD10 e CD19 em blastos leucêmicos e hematogônias." reponame:Repositório Institucional da UFC, 2005. http://www.repositorio.ufc.br/handle/riufc/1854.

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MATOS, Jesamar Correia. Análise comparativa em histograma da intensidade de fluorescência de CD10 e CD19 em blastos leucêmicos e hematogônias. 2005. 99 f. Dissertação (Mestrado em Patologia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2005.
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Hematogones are normal immature cells from bone marrow that are responsible for the production of the immune system’s B cell lineage. The acute lymphoblastic leukemia (ALL) of precursors B cells represents one type of neoplastic transformation of hematogones. Due to their high similarity there are risks of erroneous interpretation consequently making it necessary use to complementary diagnostic techniques. The CD10 and CD19 antigens are expressed on both types of cells so, it is necessary use other monoclonal antibodies to identify malign or benign nature. In attempt to avoid the use of different antibodies we investigate possible differences in the expression of CD10 and CD19 in both cell types. We collected 36 samples of bone marrow from non-neoplastic patients as a control group. The age raged from 0 to 15 years with an average of 5 years. It was also collected 39 samples from patients with ALL of B cells. The age ranged from 0 to 14 years with an average of 6.6 years. We analyzed the differences between the fluorescence intensity concerning average, standard deviation, variation, inclination and kurtosis coefficients for the two markers. The individual values of each sample were compared with the intervals generated by the values of the control group: ME±2SD; ME±2.5SD and ME±3SD. It was possible to distinguish the groups with 89.7% and 75%; 79.5% and 100% and 71.8% e 100% of sensibility and specificity, respectively for the intervals. In conclusion, the expression of CD10 and CD19 antigens on blasts and hematogones is significantly different and may be useful in the differentiation of both cell types
Hematogônias são células jovens normais da medula óssea responsáveis pela produção das células de linhagem B do sistema imunológico. A leucemia linfoblástica aguda de células precursoras B representa um dos tipos de transformação neoplásica das hematogônias. Devido a alta similaridade do ponto de vista citológico dos dois tipos celulares, é possível haver erros de interpretação na análise citológica, fazendo-se necessário em algumas circunstâncias o uso de técnicas complementares diagnósticas para diferenciar as células benignas das malignas. O uso de marcadores imunológicos através de anticorpos monoclonais marcados com fluorescência tem grande aplicabilidade nos laboratórios especializados como rotina no estudo das leucemias. Os antígenos CD10 e CD19 estão expressos em ambos os tipos celulares de forma que se faz necessária uma extensão no uso de outros marcadores para caracterização da natureza benigna ou maligna das células. Testou-se possíveis diferenças nas curvas de expressão de CD10 e CD19 dos dois tipos celulares. Foram colhidas 36 amostras de medula óssea de pacientes pediátricos não neoplásicos como grupo controle. A idade variou de 24 dias de vida a 15 anos com uma média de 5 anos. Foram colhidas também 39 amostras de pacientes portadores de LLA de linhagem B por ocasião do diagnóstico. A idade variou de 4 meses a 14 anos com uma média de 6,6 anos. Analisou-se as diferenças nas distribuições quanto a intensidade de fluorescência pelas médias, desvios-padrão, coeficientes de variação, coeficientes de inclinação e coeficiente de curtose para os dois marcadores CD10 e CD19 nos dois grupos. Os valores individuais de cada amostra foram comparados com os intervalos gerados pelos valores do grupo controle com os seguintes respectivos resultados de sensibilidade e especificidade: 89,7% e 75% para um cut-off de média+2DP; 79,5% e 100% para média+2,5DP; e 71,8% e 100% para média+3DP. Conclusão: A expressão de CD10 e CD19 em blastos e hematogônias é diferente podendo ser de utilidade prática na distinção entre os dois tipos celulares

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27

Qubaja, Marwan. "Heterogeneity of monocytes and monocyte-derived cells in human lymph nodes and bone marrow." Paris 6, 2008. http://www.theses.fr/2008PA066226.

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Rappel des faits: les monocytes humains dérivent de la moelle osseuse à partir d'un progéniteur myéloïde commun, et migrent dans la circulation sanguine. Les monocytes sont capables de se différencier en cellules effectrices morphologiquement et fonctionnellement hétérogènes, tels les macrophages et les cellules dendritiques. Basé sur l’expression de CD14 et CD16, les monocytes sanguins se répartissent entre une population majoritaire CD14highCD16- et deux populations minoritaires CD14highCD16+ et CD14dimCD16+. Objectif: Nous avons étudié l'hétérogénéité des monocytes et des cellules dérivées des monocytes, à l’état réactionnel et tumoral, dans la moelle osseuse et les ganglions lymphatiques humains à l’aide des marqueurs dérivés des monocytes/macrophages analysables sur tissu fixé et inclus en paraffine. Matériel et Méthodes: Nous avons ainsi analysé une série de 33 biopsies ostéomédullaires (BOMs) dont 8 BOMs normales, 15 cas de leucémie myélomonocytaire chronique (LMMC) et 10 cas de leucémie myéloïde chronique (LMC). Nous avons également étudié une série de 27 biopsies ganglionnaires lymphatiques dont 15 biopsies de lymphadénites réactionnelles et 12 biopsies de lymphome diffus à grandes cellules B (DLBCL). Nous avons évalué, sur toutes les séries, l'expression des marqueurs suivants: MPO, CD68 (KP1 and PG-M1), CD15, Glycophorin C, CD14, CD16, CD169, CD163, DC-SIGN, CD1a, CD11c, et CD123. Résultats: Sur les BOMs normales, nous avons clairement identifié des monocytes CD14+ dont les noyaux étaient mono ou bilobés, très difficile à distinguer morphologiquement de certains polynucléaires neutrophiles. Ces monocytes CD14+ n’exprimaient pas PG-M1 et CD163 sur tissu fixé. Les monocytes CD16+ étaient extrêmement rares sur les BMBs normales. Les macrophages médullaires et les granulocytes étaient CD14-. Nous avons montré une expansion significative des monocytes CD14+ dans la LMMC par rapport à la LMC et aux BOMs normales mais ces monocytes restent dispersés de façon interstitielle sans plages tumorales, et les monocytes CD16+ restaient exceptionnels. Nous avons également montré une diminution significative du nombre des granulocytes exprimant MPO, CD15 et CD16 dans la LMMC, probablement liée à la dysgranulopoïèse souvent rencontrée dans cette maladie. Dans les ganglions lymphatiques réactionnels, nous avons montré que la plupart des histiocytes sinusaux exprimaient CD14, CD16, CD169, et DC-SIGN. Toutefois, les histiocytes des sinus avec erythrophagocytose étaient CD14-, mais exprimait CD169 et CD16. CD163 et CD11c marquait de façon hétérogène les histiocytes des sinus et quelques rares cellules dans le centre germinatif ayant la morphologie des cellules dendritiques. Dans les ganglions lymphatiques de la maladie de Kikuchi Fujimoto, nous avons démontré une forte expansion du nombre des cellules dérivées des monocytes MPO+, et de nombreuses cellules étaient également positives pour CD123, CD14, CD163 et CD11c. Dans les DLBCL, nous avons observé une forte expansion des cellules dérivées des monocytes CD14+, sauf dans les cas associés à de nombreuses mitoses, corps apoptotiques, et macrophages à corps tingible. Nous n'avons montré aucune augmentation en nombre des cellules dérivées des monocytes exprimant CD169, CD1a ou DC-SIGN. Conclusion: Nous avons démontré que l’immunomarquage anti-CD14 permet d'identifier clairement la population monocytaire minoritaire sur la BOM normale et représente une aide utile au diagnostic histopathologique de la LMMC, probablement liée à l'expansion de la sous-population monocytaire CD14+CD16-. Nous avons également démontré l'hétérogénéité morphologique et phénotypique des cellules dérivées des monocytes dans les ganglions lymphatiques humains. Dans les ganglions réactionnels, les histiocytes des sinus sont CD14+CD16+ alors que les histiocytes sinusaux avec erythrophagocytose sont CD14-CD16+. Le DLBCL est associé à la présence de nombreuses cellules dérivées des monocytes CD14+ sauf dans les cas où se trouvent de nombreuses mitoses et des macrophages à corps tingible. Que ces changements phénotypiques soient dus au recrutement d'une sous-population monocytaire différente (CD14+CD16-, CD14-CD16+) ou à une diminution d’expression de récepteurs au sein d’une même sous-population reste à démontrer. Cependant, ces phénotypes sont probablement associés aux fonctions effectrices différentielles de ces cellules dérivées des monocytes
Background: Human monocytes originate in the bone marrow from a common myeloid progenitor, and they are then released into the peripheral blood. Circulating monocytes are capable of differentiating into morphologically and functionally heterogeneous effector cells, including macrophages and dendritic cells. Based on CD14 and CD16 expression, human peripheral blood monocytes can be divided into a major CD14highCD16- population and two minor CD14highCD16+ and CD14dimCD16+ subpopulations. Objective: We aimed to study the heterogeneity of monocytes and monocyte-derived cells in human bone marrow and lymph nodes, in reactive and tumoral states, with the help of new monocyte/macrophage-derived markers evaluable on paraffin-embedded tissue. Materials and Methods: For this purpose, we studied a series of 33 bone marrow biopsies (BMBs) consisted of 8 normal BMBs, 15 cases of chronic myelomonocytic leukemia (CMML) and 10 cases of chronic myeloid leukemia (CML). We also studied a series of 27 lymph node biopsies including 15 biopsies of reactive lymph nodes and 12 diffuse large B cell lymphoma (DLBCL) nodal biopsies. We evaluated the expression of the following markers on bone marrow and lymph node biopsies: MPO, CD68 (KP1 and PG-M1), CD15, Glycophorin C, CD14, CD16, CD169, CD163, DC-SIGN, CD1a, CD11c, and CD123. Results: In normal BMBs, we clearly identified CD14+ monocytes with mono or bilobated nuclei, very difficult to differentiate from some neutrophils on morphology. These CD14+ monocytes were negative for PG-M1 and CD163. CD16+ monocytes were extremely rare on normal BMBs. Medullary macrophages and granulocytes were CD14-. We showed a significant expansion of dispersed CD14+ monocytes in CMML compared to CML and normal BMBs, but no increase in CD16+ monocytes. We also showed a significant decrease in the number of granulocytes expressing MPO, CD15 and CD16 in CMML, probably related to dysgranulopoiesis often encounterd in this disease. In reactive human lymph nodes, we showed that most sinusoidal histiocytes were strongly positive for CD14, CD16, CD169, and DC-SIGN. CD163 and CD11c variably stained sinusoidal histiocytes and a few cells in the germinal center having the morphology of dendritic cells. However, sinusoidal histiocytes with erythrophagocytosis lacked CD14, but expressed CD16 and CD169. In the lymph nodes of Kikuchi Fujimoto’s disease, we demonstrated a strong expansion of the number of MPO+ monocyte-derived cells, and numerous monocyte-derived cells were also positive for CD123, CD14, CD11c and CD163. In DLBCL, we demonstrated a strong expansion of CD14+ monocyte-derived cells, except in cases associated with numerous mitosis, apoptotic bodies, and tingible body macrophages. We showed no increase in number of monocyte-derived cells positive for CD169, CD1a or DC-SIGN. Conclusion: We demonstrated that CD14 immunostaining makes it possible to clearly identify the rare monocyte population on normal BMBs and this is therefore useful for the histopathological diagnosis of CMML, being probably mainly associated with the expansion of the CD14+CD16- monocyte subpopulation. We also demonstrated the morphological and phenotypical heterogeneity of monocyte-derived cells in human lymph nodes. In reactive human lymph nodes, sinusoidal histiocytes are CD14+CD16+ whereas these sinusoidal histiocytes with erythrophagocytosis are CD14-CD16+. DLBCL is associated with the presence of numerous CD14+ monocyte-derived cells except in cases where numerous mitosis and tingible body macrophages are found. Whether these phenotypical changes are due to the recruitment of a different monocyte subpopulation (CD14+CD16-, CD14-CD16+) or to a downregulation of some receptors remains to be demonstrated. However, these changes are probably linked to the differential effector functions of these monocyte-derived cells

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Hjelle, Kjersti Marie. "Do Serglycin Related Alterations of Thrombocytes and Myeloid Cells Affect Tumor Progression and Behavior." Thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-259136.

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Investigation of tumor growth has traditionally been studied focusing only on the cancer cells. However, tumors consist of a complex tissue organization where heterotypic signaling occurs between different cell types. The cross-talk between tumor cells and other surrounding cell types may ultimately prove to be as important for the tumor cell behavior as the internal signaling cascades in the tumor cell itself.Myeloid cells, such as granulocytes and monocytes, and thrombocytes play an important role in the tumor tissue, as a tumor can be compared to a wound healing process without the normal regulation mechanisms. Platelets are thought to facilitate tumor cell extravasation by binding to the tumor cell and recruiting myeloid cells that secrete factors aiding tumor migration through the endothelial cells. Studying the content of granules and vesicles of the platelets and myeloid cells can provide important knowledge about how the tumor interactions are mediated and which key proteins that controls these processes.Serglycin is an intracellular proteoglycan that attaches chains of negatively charged glycosaminoglycans. It is thought to have a function in retaining and storing proteins in hematipoietic cells. In this project the impact of the loss of serglycin on platelets and myeloid cells was investigated, using a spontaneous insulinoma serglycin knockout mouse model. The results suggests that serglycin does not affect the amount of neutrophil granulocytes and monocytes in peripheral blood, nor does it seem to affect the amount of platelets sequestered to the tumor tissue. A co-staining for platelets and MMP9 positive granulocytes was also performed in order to assess if granulocyte-platelet interactions in the tumor were affected by loss of serglycin. Interactions between these cells were observed in both genotypes. Von Willebrand factor levels in the tumor tissue also remained unchanged upon loss of serglycin. However, preliminary experiments indicated that serglycin seems to play a role in the intracellular amounts of vimentin and VEGFB in undifferentiated primary bone marrow derived monocytes.

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Fritzen, Anna [Verfasser]. "Vergleichende Studien zur Rolle der Tetraspanine CD9, CD81 und CD151 im Infektionsweg des Humanen Papillomvirus Typ 16 / Anna Fritzen." Mainz : Universitätsbibliothek der Johannes Gutenberg-Universität Mainz, 2020. http://d-nb.info/1224810295/34.

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Pinheiro, CatiÃssia Dantas. "CÃlulas CD3+, CD4+, CD8+, CD3-CD16+CD56+ e CD19+ em sangue perifÃrico de pacientes com hansenÃase e indivÃduos saudÃveis." Universidade Federal do CearÃ, 2013. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=16323.

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Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico
A hansenÃase Ã uma doenÃa granulomatosa, infecto-contagiosa causada pelo Mycobacterium leprae. Trata-se de uma infecÃÃo crÃnica com amplo espectro de respostas imunes celulares em humanos. Possui alto poder infectante e baixo poder patogÃnico. Este estudo tem como objetivo quantificar e comparar leucÃcitos e subpopulaÃÃes de linfÃcitos T totais (CD3+), T auxiliares (CD3+CD4+), T citotÃxicos (CD3+CD8+), B (CD19+) e NK (CD3-CD16+CD56+) em sangue perifÃrico de indivÃduos com hansenÃase e controles saudÃveis. Os pacientes foram provenientes do Centro de Dermatologia D. LibÃnia, Fortaleza-CE, Brasil. A determinaÃÃo do nÃmero de linfÃcitos em cada subpopulaÃÃo foi realizada por citometria de fluxo. A anÃlise estatÃstica foi realizada pelo programa GraphPad Prism 5.0 para Windows com significÃncia estabelecida para valores de p<0,05. Ã um estudo do tipo caso controle de carÃter observacional, realizado a partir da anÃlise do sangue perifÃrico de indivÃduos com diagnÃstico de hansenÃase e de indivÃduos saudÃveis. A populaÃÃo de pacientes com hansenÃase, sem tratamento foi composta de 15 pessoas. A populaÃÃo de controles saudÃveis foi composta por 29 pessoas. As mÃdias das contagens de LinfÃcitos NK (CD3-CD16+CD56+) no grupo de pacientes com hansenÃase e nos controles saudÃveis, dadas em cÃlulas/mm3, foram, 147(Â113,4) e 378,1 (Â231,7) respectivamente, p = 0,0008. As mÃdias das contagens de LinfÃcitos B (CD19+) no grupo de pacientes com hansenÃase e nos controles saudÃveis, dadas em cÃlulas/mm3, foram, 233,3 (Â85,89) e 115,3 (Â53,01) , respectivamente, p < 0,0001. NÃo foram encontradas diferenÃas estatÃsticas significantes entre as amostras de leucÃcitos, de linfÃcitos T CD3+, linfÃcitos T CD4+ e linfÃcitos T CD8+. Os dados do presente estudo sinalizam que as cÃlulas NK parecem desempenhar papel de relevÃncia na resposta ao M. leprae. O linfÃcito B jÃ ocupa papel de destaque na resposta imunolÃgica ao M. leprae, sobretudo nas formas lepromatosas, e este estudo reforÃa a importÃncia destas cÃlulas.
Leprosy is an infectious and granulomatous disease caused by Mycobacterium leprae. The aim of this study was to quantify and compare levels of leucocytes and lymphocyte subpopulations (CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD3-CD16+CD56+) in peripheral blood of patients with leprosy and healthy controls. Patients were followed at Centro de Dermatologia D. LibÃnia, Fortaleza-CE, Brasil. Flow cytometry was used to determine numbers of lymphocytes. Statistical analisys was done with GraphPad Prism 5.0 software for windows. P values under 0.05 were considered siginificant.This was an observational case-control study. Fifteen leprosy patients without treatment were evaluated and 29 healthy individuals were included in control group. NK cells (CD3-CD16+CD56+) mean in leprosy patients was 147(Â113,4) and in controls was 378,1 (Â231,7). Comparisson stablished a p value of 0.0008. B lymphocytes (CD19+) mean in leprosy patients was 233,3 (Â85,89) and in controls was 115,3 (Â53,01), with p < 0,0001 . No differences were observed in CD3+ T lymphocytes, CD4+ T lymphocytes and CD8+ T lymphocytes. This study suggests that NK cells may play a role in innate response to M. leprae.

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Pinheiro, Catiússia Dantas. "Células CD3+, CD4+, CD8+, CD3-CD16+CD56+ e CD19+ em sangue periférico de pacientes com hanseníase e indivíduos saudáveis." reponame:Repositório Institucional da UFC, 2013. http://www.repositorio.ufc.br/handle/riufc/15425.

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PINHEIRO, Catiússia Dantas. Células CD3+, CD4+, CD8+, CD3-CD16+CD56+ e CD19+ em sangue periférico de pacientes com hanseníase e indivíduos saudáveis. 2013. 65 f. Dissertação (Mestrado em Patologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2013.
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Leprosy is an infectious and granulomatous disease caused by Mycobacterium leprae. The aim of this study was to quantify and compare levels of leucocytes and lymphocyte subpopulations (CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD3-CD16+CD56+) in peripheral blood of patients with leprosy and healthy controls. Patients were followed at Centro de Dermatologia D. Libânia, Fortaleza-CE, Brasil. Flow cytometry was used to determine numbers of lymphocytes. Statistical analisys was done with GraphPad Prism 5.0 software for windows. P values under 0.05 were considered siginificant.This was an observational case-control study. Fifteen leprosy patients without treatment were evaluated and 29 healthy individuals were included in control group. NK cells (CD3-CD16+CD56+) mean in leprosy patients was 147(±113,4) and in controls was 378,1 (±231,7). Comparisson stablished a p value of 0.0008. B lymphocytes (CD19+) mean in leprosy patients was 233,3 (±85,89) and in controls was 115,3 (±53,01), with p < 0,0001 . No differences were observed in CD3+ T lymphocytes, CD4+ T lymphocytes and CD8+ T lymphocytes. This study suggests that NK cells may play a role in innate response to M. leprae.
A hanseníase é uma doença granulomatosa, infecto-contagiosa causada pelo Mycobacterium leprae. Trata-se de uma infecção crônica com amplo espectro de respostas imunes celulares em humanos. Possui alto poder infectante e baixo poder patogênico. Este estudo tem como objetivo quantificar e comparar leucócitos e subpopulações de linfócitos T totais (CD3+), T auxiliares (CD3+CD4+), T citotóxicos (CD3+CD8+), B (CD19+) e NK (CD3-CD16+CD56+) em sangue periférico de indivíduos com hanseníase e controles saudáveis. Os pacientes foram provenientes do Centro de Dermatologia D. Libânia, Fortaleza-CE, Brasil. A determinação do número de linfócitos em cada subpopulação foi realizada por citometria de fluxo. A análise estatística foi realizada pelo programa GraphPad Prism 5.0 para Windows com significância estabelecida para valores de p<0,05. É um estudo do tipo caso controle de caráter observacional, realizado a partir da análise do sangue periférico de indivíduos com diagnóstico de hanseníase e de indivíduos saudáveis. A população de pacientes com hanseníase, sem tratamento foi composta de 15 pessoas. A população de controles saudáveis foi composta por 29 pessoas. As médias das contagens de Linfócitos NK (CD3-CD16+CD56+) no grupo de pacientes com hanseníase e nos controles saudáveis, dadas em células/mm3, foram, 147(±113,4) e 378,1 (±231,7) respectivamente, p = 0,0008. As médias das contagens de Linfócitos B (CD19+) no grupo de pacientes com hanseníase e nos controles saudáveis, dadas em células/mm3, foram, 233,3 (±85,89) e 115,3 (±53,01) , respectivamente, p < 0,0001. Não foram encontradas diferenças estatísticas significantes entre as amostras de leucócitos, de linfócitos T CD3+, linfócitos T CD4+ e linfócitos T CD8+. Os dados do presente estudo sinalizam que as células NK parecem desempenhar papel de relevância na resposta ao M. leprae. O linfócito B já ocupa papel de destaque na resposta imunológica ao M. leprae, sobretudo nas formas lepromatosas, e este estudo reforça a importância destas células.

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Williams, Dionna Whitney. "Characterization of mechanisms that contribute to the transmigration of CD14+CD16+ monocytes across the blood brain barrier| Implications for neuroaids." Thesis, Yeshiva University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3580306.

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HIV associated neurocognitive disorders (HAND) encompass a spectrum of cognitive deficits that affect 40-70% of HIV-infected individuals, despite antiretroviral therapy. Monocytes are among the first cells infected by HIV and are critical mediators of HAND as they facilitate viral seeding of the central nervous system (CNS) upon their transmigration across the blood brain barrier (BBB). Monocyte subpopulations exist with differing levels of maturation and functions. Monocytes that express CD14, the LPS receptor, and CD16, the Fcylll receptor, are a mature population of cells that are highly susceptible to HIV. While CD14⁺CD16⁺ monazites are believed to mediate the neuropathogenesis of HIV, little is known about the mechanisms that contribute to their diapedesis across the BBB. As the CD14⁺CD16⁺ monocyte represents a small percentage of monocytes in healthy individuals, we developed a tissue culture model to enrich for this population. We found that there was a selective transmigration of CD14⁺CD16⁺ monocytes across our BBB model, with little migration of other monocyte populations. HIV infection resulted in the increased transmigration of CD14⁺CD16⁺ monocytes in response to CCL2 relative to uninfected cells, which was due to increased CCR2 and a heightened sensitivity to the chemokine. The junctional proteins JAM-A and ALCAM were also critical for this transmigration as antibody blockade reduced the number of migrating monocytes. These CD14+CD16+ monocytes were present in significantly greater numbers in HIV-infected people, despite viral suppression, in contrast to individuals without HIV. CCR2 was increased on CD14⁺CD16⁺ monocytes in HIV-infected individuals with HAND compared to those with normal cognition and was predictive of fluctuations in cognitive impairment upon longitudinal study. ALCAM and JAM-A were increased on CD14⁺CD16⁺ monocytes in those with HIV compared to HIV seronegative people. Blocking antibodies to ALCAM and JAM-A inhibited the transmigration of CD14⁺CD16⁺ monocytes, but not of T cells, suggesting their importance in specifically facilitating monocyte transmigration across the BBB. Our findings indicate therapeutic strategies to monitor HAND, and that may decrease the entry of CD14⁺CD16⁺ monocytes into the CNS of HIV-infected individuals, contributing to the eradication of neuroinflammation, HAND, and CNS viral reservoirs.

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Vilela, Maria Helena Tavares. "Ki-67, cd10, cd34, p53, cd117 e mastócitos no diagnóstico diferencial dos fibroadenomas celulares e na graduação dos tumores filóidesz." Universidade Federal de Goiás, 2013. http://repositorio.bc.ufg.br/tede/handle/tede/3229.

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The proper management of breast phyllodes tumors (PTs) remains challenging, due to the difficulty of the correct preoperative diagnosis. The aim of this study was to evaluate the usefulness of the Ki-67, CD10, CD34, p53, CD117 and the number of mast cells for the differential diagnosis between benign PTs and cellular fibroadenomas (CFs), and also at the grading of PTs. 51 primary PTs and 14 FCs were examined by immunohistochemistry (IH). Through the evaluation of the expression of CD117, greater epithelial expression was found at the FCs and an increased number of mast cells in benign TFs. The stromal expression of the Ki-67, CD10, CD34 and p53 showed relevance to the grading of PTs.
O manejo adequado dos tumores filóides (TFs) mamários continua desafiador, devido à dificuldade do diagnóstico pré-operatório correto. O objetivo deste estudo foi avaliar a utilidade do Ki-67, do CD34, do CD10, do CD117, da p53 e do número de mastócitos no diagnóstico diferencial entre os TFs benignos e fibroadenomas celulares (FCs), bem como na graduação dos TFs. Foram examinados 51 TFs primários e 14 FCs por imunohistoquímica (IH). Na marcação pelo CD117, houve maior expressão epitelial nos FCs e maior número de mastócitos nos TFs benignos. A expressão estromal do Ki-67, da p53, do CD10 e CD34 mostrou-se significante na graduação dosTFs.

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Ferreira, André Costa. "O papel da integrina CD11d/CD18 na diferenciação e ativação de acrófagos: Efeitos de heme e hemozoína sintética na resposta imune." Instituto Oswaldo Cruz, 2012. https://www.arca.fiocruz.br/handle/icict/6401.

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Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.
A malária é uma doença parasitária causada por protozoários do gênero Plasmodium e representa um grande problema de saúde pública. Sabe-se que metade da população mundial vive em áreas endêmicas, onde esta doença gera cerca de 500 milhões de casos clínicos e em torno de 1 milhão de mortes anualmente. O processo infeccioso da malária é desencadeado por uma resposta imunoinflamatória exacerbada do hospedeiro caracterizada por migração e acúmulo de leucócitos, produção de citocinas pró-inflamatórias e mediadores químicos. Neste processo, as leucointegrinas exercem um papel extremamente importante mediando a adesão, migração e sinalização celular. Neste grupo de integrinas, a CD11d/CD18, que foi descrita mais recentemente está envolvida em diversos eventos patológicos como aterosclerose, dano neuronal e outros. Resultados preliminares de nosso grupo mostraram que animais deficientes (CD11d-/-) para esta integrina apresentam uma maior sobrevida à infecção com Plasmodium berghei Anka (PbA). Entretanto, ainda não se conhece o papel desta integrina na fisiopatologia da malária. O presente trabalho mostrou que a integrina CD11d/CD18 é dinamicamente expressa em macrófagos diferenciados da medula óssea de animais infectados com PbA. Ensaios in vitro com essas células, demonstraram que esta integrina não afeta a capacidade proliferativa dessas células. Além disso, avaliamos parâmetros importantes para a ativação celular, como produção de espécies reativas de oxigênio e citocinas pró- e anti-inflamatórias. Observamos que macrófagos de animais CD11d-/- produzem quantidades significantemente mais baixas de malondialdeído e de TNF- , e níveis altos de IL-10 em relação aos macrófagos de animais CD11d+/+. Além disso, a produção de prostaglandina E2 foi significantemente diminuída em macrófagos provenientes de animais CD11d-/-. Esses dados indicam que a integrina possui um papel importante na modulação da resposta imune. Verificamos ainda que macrófagos de animais CD11d-/- apresentaram uma diminuição na sua capacidade fagocítica de hemácias parasitadas em relação aos macrófagos de animais CD11d+/+. Entretanto, a ausência desta integrina não afetou a capacidade destes macrófagos de fagocitar hemozoína sintética (sHz). Estes resultados juntos sugerem que a integrina CD11d está envolvida no processo de ativação celular dos macrófagos, modulando a resposta imune do hospedeiro na fisiopatologia da malária, o que torna esta molécula um potencial alvo para ações terapêuticas.
Malaria is a parasitic disease caused by protozoa of the genus Plasmodium and is a major public health problem. It is known that half the world population lives in endemic areas where this disease causes about 500 million clinical cases and around 1 million deaths annually. The process of malaria infection is initiated by a host immunoinflammatory response exacerbated characterized by the migration and accumulation of leukocytes, the production of proinflammatory cytokines and chemical mediators. In this process, leukointegrins play a very important role in mediating adhesion, migration and cell signaling. In this group of integrins, CD11d/CD18, which has been described more recently, is involved in gravel pathological events such as atherosclerosis, neuronal damage and others pathologies. Preliminary results from our group have shown that animals deficient (CD11d-/-) for this integrin have a higher survival to infection with Plasmodium berghei Anka (PbA). However, we still do not know the role of CD11d/CD18 integrin in the pathophysiology of malaria. The present study demonstrated that the integrin is dynamically expressed in differentiated bone marrow macrophages from animals infected with PbA. Experiments with these cells in vitro have demonstrated that the integrin does not affect the proliferative capacity of these cells. Furthermore, we evaluated parameters important to cellular activation, such as production of reactive oxygen species, proinflammatory and anti-inflammator cytokines. Observed that macrophages, from deficient mice for the integrin CD11d-/-, produce significantly lower amounts of malondialdehyde and TNF- , and high levels of IL-10 in relation to the macrophages from animals CD11d+/+. Furthermore, the production of prostaglandin E2 was significantly reduced by macrophages from animals CD11d-/-. These data indicate that integrin plays an important role in modulating the immune response. Also verified that macrophages from animals CD11d-/- showed a decrease in their phagocytic ability of infected erythrocytes to macrophages compared to animals CD11d+/+. However, absense of this integrin did not affect the ability of macrophages to phagocytize synthetic hemozoin – sHz. These results together suggest that CD11d integrin is involved in cellular activation of macrophages by modulating the host immune response in the pathophysiology of malaria, which makes this molecule a potential target for therapeutic actions.

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Kraus, Stephan Georg. "Funktionelle Charakterisierung von CD16+ Monozytensubpopulationen." Doctoral thesis, Universitätsbibliothek Leipzig, 2011. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-77454.

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Seit 20 Jahren unterteilt man Monozyten in eine klassische CD14++/CD16-Population und eine proinflammatorische CD16+ Population. Letztere macht 10-20 % der peripheren Blutmonozyten aus und ist unter verschiedenen pathologischen Zuständen drastisch erhöht. Seit Kurzem wird die CD16+ Fraktion in zwei weitere Untergruppen aufgeteilt, die CD14++/CD16+ und die CD14+/CD16+ Monozyten. In der hier vorliegenden Arbeit wurde versucht, die relativ neue und wenig charakterisierte Subpopulation der CD14++/CD16+ Monozyten näher zu beschreiben. Es sollte die Frage beantwortet werden, ob diese sich von den übrigen Subpopulationen abzugrenzen lässt und damit als eigenständige Zellgruppe anzusehen ist. Die von gesunden Spendern gewonnen peripheren mononukleären Blutzellen (PBMCs) wurden mithilfe einer Magnetsäulenvorseparation von einem Großteil der T-, B- und NK-Zellen befreit. Die restlichen Zellen wurden mit Anti-CD14-FITC und Anti-CD16-PE markiert. In einem Hochgeschwindigkeitssortierer wurden diese, anhand ihres Fluoreszenzmusters, in die drei Subpopulationen CD14++/CD16- (Sub1), CD14++/CD16+ (Sub2) und CD14+/CD16+ (Sub3) aufgeteilt. Durch dieses Verfahren konnte ein hoher Reinheitsgrad erreicht werden. Die erhaltenen Subpopulationen wurden mit heterologen CD4+ T-Lymphozyten zusammen gebracht. Die Reaktion dieser T-Zellen auf die verschiedenen Subpopulationen wurde im Proliferations- und Sekretionsassay (IFN-γ, IL-4) studiert. Des Weiteren wurde die Zytokinsekretion der Monozytenarten nach definierter Stimulierung (LPS, Zymosan, aktivierte T-Zellen) analysiert. In einem zweiten Versuchskomplex wurden aus den jeweiligen Subpopulationen unreife dendritische Zellen (Sub-DCs) differenziert und diese auf bestimmte Oberflächenmarker bzw. deren Verhalten mit heterologen CD4+ T-Zellen im Proliferations-/Sekretionsassay (IFN-γ, IL-4) untersucht. Nach 7 Tagen Inkubation fanden sich im Sub2- und Sub3-Ansatz ca. 10 % mehr proliferierende T-Zellen als im Sub1-Ansatz. Dabei lag der Anteil der CD25+ T-Zellen in diesen beiden Versuchsansätzen ebenfalls um 10 % höher. Der Proliferationsassay über 14 Tage zeigte für die Sub3 ca. 10-15 % mehr proliferierende T-Zellen als für die anderen Populationen. Das Niveau der CD25-Expression der T-Zellen war hierbei in allen drei Ansätzen gleich. Im Sekretionsassay induzierten alle drei Subpopulationen eine Th1-Antwort, jedoch mit einem leicht höheren Anteil IFN-γ-positiver T-Zellen für die CD16+ Monozyten. Durch LPS-Gabe produzierten die CD14+/CD16+ Monozyten am meisten TNF-α, gefolgt von den CD14++/CD16+. Bei den CD14++/CD16- fanden sich die geringsten Mengen an TNF-α. Zusammen mit aktivierten T-Zellen demonstrierten die CD14++/CD16+ Monozyten die stärkste TNF-α-Sekretion unter allen anderen Subpopulationen. Für die beiden CD16+ Populationen wurden nach LPS-Stimulation höhere Werte für IL-1β bestimmt als für die klassischen Monozyten. Sowohl im LPS- als auch im Zymosanansatz lag die IL-6-Sekretion der CD14++/CD16- Subpopulation über der der anderen zwei Fraktionen. Unter allen drei Stimuli wurden die höchsten Werte für IL-8 bei den CD14++/CD16- Monozyten detektiert, gefolgt von den CD14++/CD16+. Am niedrigsten lag die IL-8-Produktion bei den CD14+/CD16+. Die IL-10-Sekretion im LPS- und im Zymosanansatz der CD14++/CD16- und CD14++/CD16+ Monozyten war gegenüber der CD14+/CD16+ Subpopulation erhöht. Nach Entwicklung der unreifen dendritischen Zellen aus den entsprechenden Monozytenarten weisen diese eine differenzierte Morphologie auf. Die DCs der CD14+/CD16+ Monozyten hatten eine stärkere HLA-DR-Expression in der mittleren Fluoreszenzintensität als die anderen beiden Sub-DC-Populationen, wobei sich keine Unterschiede in der HLA-DRExpressionsintensität zwischen Sub1- und Sub2-DCs feststellen ließen. Der Anteil der CD11c positiven Zellen war bei den Sub1-DCs deutlich größer als bei den Sub2-DCs. Dagegen exprimierten die Sub3-DCs praktisch kein CD11c. Im Proliferationsassay über 7 Tage ergaben sich keine signifikanten Differenzen zwischen den Subpopulationen. Allerdings zeigte sich eine Tendenz zu geringeren Werten im Anteil proliferierender bzw. CD25-positiver T-Lymphozyten für den Sub2-DC-Ansatz. Nach 14 Tagen im Assay war der Anteil der proliferierenden T-Zellen bei den Sub1-DCs um 10 % höher als bei den Sub2-DCs. Es fanden sich ca. 10 % mehr CD25+ T-Zellen im Sub1-DC-Ansatz als in den anderen beiden Ansätzen. Der Sekretionsassay erbrachte für alle Sub-DCs eine Th1-Induktion der T-Zellen. Dabei ließen sich keine Abweichungen im Anteil IFN-γ-positiver T-Zellen zwischen den einzelnen Sub-DC-Kulturen nachweisen. Die gewonnen Ergebnisse dieser Arbeit verdeutlichen auf der einen Seite das proinflammatorische Potential (z.B. TNF-α-Sekretion, erhöhte Proliferation), auf der anderen Seite die antiinflammatorische Komponente (IL-10-Sekretion) der CD14++/CD16+ Monozyten. Eine Rolle in der Regulation von entzündlichen und infektiologischen Erkrankungen erscheint für diese Subpopulation denkbar. Die Subpopulation 2 kann dabei als eigenständige Monozytenfraktion betrachtet werden. Die funktionellen Unterschiede zwischen den analysierten Monozytensubpopulationen zeigten sich auch nach deren Differenzierung zu unreifen dendritischen Zellen. In Anbetracht des erhöhten Anteils der CD16+ Monozyten im Rahmen diverser autoimmuner Krankheiten und der immer klarer werdenden Unterteilung in eine CD14++/CD16+ und eine CD14+/CD16+ Subpopulation, sollten weitere Untersuchungen zur klinischen Relevanz dieser Monozytengruppen durchgeführt werden. Die in der vorliegenden Arbeit erzielten Ergebnisse könnten bei der Zuordnung und Interpretation in diese zukünftigen klinischen Befunde behilflich sein
For more than 20 years monocytes were subdivided in the classical CD14++/CD16- population and the proinflammatory CD16+ populations. The latter one includes about 10-20 % of the peripheral blood monocytes and is dramatically expanded under different pathological circumstances. Recently, the CD16+ fraction was further subdivided into two subpopulations: The CD14++/CD16+ and CD14+/CD16+ monocytes. In the present paper, the subpopulation of CD14++/CD16+ monocytes was characterized in order to answer the question if this subset can be distinguished as an independent cell population. T cells, B cells and NK cells were depleted from peripheral mononuclear blood cells (PBMCs) from healthy donors using immunomagnetic cell separation. Subsequently, the pre-separated cells were stained with anti-CD14-FITC and anti-CD16-PE and separated by fluorescence activated cell sorting (FACS) in three subpopulations: The CD14++/CD16- (Sub1), the CD14++/CD16+ (Sub2) and the CD14+/CD16+ (Sub3). The achieved purity was sufficient for the subsequent experiments. The obtained subpopulations were co-cultured together with heterologous CD4+ T lymphocytes. The reaction of these T cells to the different subpopulations was studied in the proliferation and secretion assay (IFN-γ, IL-4). Furthermore, the cytokine secretion of the monocyte subsets after defined stimulation (LPS, Zymosan, activated T cells) was analysed. In a second set of experiments, immature dendritic cells were differentiated from the monocyte subpopulations (Sub-DCs) and phenotypically and functionally characterized according to the expression of cell surface markers and the response to heterologous CD4+ T cells in the proliferation/secretion assay (IFN-γ, IL-4). After 7 days of incubation, the Sub2 and Sub3 of the monocytes induced approximately 10 % higher proliferation rates of T cells than the Sub1. The resulting frequency of CD25+ T cells in these two co-culture settings was also 10 % higher. The proliferation analysis after 14 days again showed for the Sub3 ca. 10-15 % more proliferating T cells than for the other populations. At this, the frequency of CD25 expression was equal in all co-cultures. In the secretion assay all three subpopulations induced a Th1 response, but the range of IFN-γ-positive T cells was somewhat higher for the CD16+ monocytes. Under LPS stimulation the CD14+/CD16+ monocytes produced the highest amounts of TNF-α followed by the CD14++/CD16+. The CD14++/CD16- showed the lowest amounts of TNF-α. In co-culture with activated T cells the CD14++/CD16+ monocytes demonstrated the strongest TNF-α secretion from all subpopulations. After LPS stimulation, a higher level of IL-1β was measured for both CD16+ populations than for the classical monocytes. In the LPS and the Zymosan stimulated cultures, the IL-6 secretion of the CD14++/CD16- subpopulation was higher than in the two other fractions. Under all three stimuli the highest levels of IL-8 were detected for the CD14++/CD16- monocytes followed by the CD14++/CD16+. The lowest IL-8 production was found by the CD14+/CD16+. The IL-10 secretion of the CD14++/CD16- and CD14++/CD16+ monocytes was increased compared to the CD14+/CD16+ subpopulation after LPS and Zymosan stimulation. The in vitro generated immature dendritic cells from the different monocyte subsets showed a differentiated morphology. The DCs of the CD14+/CD16+ monocytes had the strongest HLA-DR expression compared to the other two Sub-DC populations. No differences in the HLA-DR intensity were found between the Sub1- and Sub2-DCs. The rate of CD11c-positive cells was significantly higher in the Sub1-DCs than in the Sub2-DCs. However, the Sub3-DCs expressed no CD11c altogether. The proliferation assay over 7 days showed no significant differences between the subpopulations. Nevertheless, a tendency for lower levels of proliferating or CD25-positive T lymphocytes was seen in T cells co-cultured with the Sub2-DC. After 14 days, the ratio of proliferating T cells was 10 % higher with the Sub1-DCs than with the Sub2-DCs. The Sub1-DC co-culture yielded ca. 10 % more CD25+ T cells than the other two. The secretion assay revealed for all Sub-DCs a Th1 response of the T cells, with no differences in the amount of IFN-γ-positive T cells between the Sub-DC cultures. The results illustrate on one hand the proinflammatory potential (e.g. TNF-α secretion, higher proliferation), on the other hand the antiinflammatory effect (IL-10 secretion) of CD14++/CD16+ monocytes. A role in the regulation of inflammatory and infectious diseases seems to be possible for this subpopulation. The subpopulation 2 can be regarded as an independent fraction of monocytes. The functional differences between the analyzed monocyte subpopulations are further underscored following differentiation into immature dendritic cells. Considering the increased proportion of CD16+ monocytes in various autoimmune diseases and their clear subdivision in a CD14++/CD16+ and a CD14+/CD16+ subpopulation, new investigations about the clinical relevance are warranted. The findings obtained in the work presented could be in the basis for these future clinical studies

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Beeck, Stefan. "Expression der Membranantigene CD14, CD16, HLA-DR sowie der Toll-Like-Rezeptoren TLR2, TLR3 und TLR4 auf Blutmonozyten von Patienten mit Nierenerkrankungen." Diss., lmu, 2010. http://nbn-resolving.de/urn:nbn:de:bvb:19-115488.

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Berti, Verena Dorothea [Verfasser], and Karlheinz [Akademischer Betreuer] Peter. "Die molekulare MR-Bildgebung des Monozytenintegrins Mac-1 (CD11b/CD18) optimiert nicht die Detektion von Monozyten in atherosklerotischen Plaques von ApoE−/−-Mäusen." Freiburg : Universität, 2011. http://d-nb.info/1123460205/34.

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Thieblemont, Nathalie. "Role des recepteurs cr1 (cd35) et cr3 (cd11b/cd18) dans la penetration et la replication du virus de l'immunodeficience humaine (vih) dans les monocytes/macrophages." Paris 6, 1993. http://www.theses.fr/1993PA066651.

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Nous avons demontre que les glycoproteines recombinantes gp160 et gp120 du vih1 activent le complement humain en l'absence d'anticorps. Les glycoproteines gp160 et gp120 induisent un clivage de c3 dans du serum humain normal. Ce clivage est lie a une activation de la voie classique du complement qui peut etre augmente en presence d'anticorps anti-vih1. Cette activation du complement permet aussi une opsonisation des particules virales puisque l'infection de cellules cibles par le vih1 ou le vih2 peut etre facilitee par une pre-incubation du virus dans du serum humain normal. La pre-incubation des cellules avec des anticorps anti-cr1 ou anti-cr3 inhibe l'infection des cellules des lignees pro-monocytaires, comme des monocytes, indiquant que la penetration du virus s'effectue par l'intermediaire des recepteurs cr1 (cd35) et cr3 (cd11b/cd18). L'infection mediee par les molecules cr1 et cr3 se produit independamment des molecules cd4. Nos etudes montre par ailleurs que la stimulation des recepteurs du complement induit simultanement dans les cellules infectees, une translocation du nf-kappab, une augmentation de la replication virale et une deregulation de la synthese des cytokines. Cette deregulation pourrait etre une consequence d'une anomalie de maturation des cellules. D'autre part, nous avons identifie l'apparition chez les patients infectes par le vih d'une sous-population de monocytes plus matures dont l'emergence dependrait de la deregulation de l'equilibre des cytokines lymphocytaires

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Martins, Soraia Alexandra Araújo. "CD81 interacting proteins." Master's thesis, Universidade de Aveiro, 2016. http://hdl.handle.net/10773/16139.

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Mestrado em Biomedicina Molecular
Fertilization is a multistep and complex process culminating in the merge of gamete membranes, cytoplasmic unity and fusion of genome. CD81 is a tetraspanin protein that participates in sperm-oocyte interaction, being present at the oocyte surface. CD81 has also been implicated in other biological processes, however its specific function and molecular mechanisms of action remain to be elucidated. The interaction between CD81 and its binding partner proteins may underlie the CD81 involvement in a variety of cellular processes and modulate CD81/interactors specific functions. Interestingly, in a Yeast two Hybrid system previously performed in our lab, CD81 has emerged as a putative interactor of the Amyloid Precursor Protein (APP). In the work here described, bioinformatics analyses of CD81 interacting proteins were performed and the retrieved information used to construct a protein-protein interaction network, as well as to perform Gene Ontology enrichment analyses. CD81 expression was further evaluated in CHO, GC-1 and SH-SY5Y cell lines, and in human sperm cells. Additionally, its subcellular localization was analyzed in sperm cells and in the neuronal-like SH-SY5Y cell line. Subsequently, coimmunoprecipitation assays were performed in CHO and SH-SY5Y cells to attempt to prove the physical interaction between CD81 and APP. A functional interaction between these two proteins was accessed thought the analyses of the effects of CD81 overexpression on APP levels. A co-localization analysis of CD81 and some interactors proteins retrieved from the bioinformatics analyses, such as APP, AKT1 and cytoskeleton-related proteins, was also performed in sperm cells and in SH-SY5Y cells. The effects of CD81 in cytoskeleton remodeling was evaluated in SH-SY5Y cells through monitoring the effects of CD81 overexpression in actin and tubulin levels, and analyzing the colocalization between overexpressed CD81 and F-actin. Our results showed that CD81 is expressed in all cell lines tested, and also provided the first evidence of the presence of CD81 in human sperm cells. CD81 immunoreactivity was predominantly detected in the sperm head, including the acrosome membrane, and in the midpiece, where it co-localized with APP, as well as in the post-acrosomal region. Furthermore, CD81 co-localizes with APP in the plasma membrane and in cellular projections in SH-SY5Y cells, where CD81 overexpression has an influence on APP levels, also visible in CHO cells. The analysis of CD81 interacting proteins such as AKT1 and cytoskeletonrelated proteins showed that CD81 is involved in a variety of pathways that may underlie cytoskeleton remodeling events, related to processes such as sperm motility, cell migration and neuritogenesis. These results deepen our understanding on the functions of CD81 and some of its interactors in sperm and neuronal cells.
A fecundação é um processo complexo e faseado que culmina na fusão celular das membranas dos gametas, do citoplasma e do genoma. A CD81 é uma proteína tetraspanina que participa na interacção espermatozóide-oócito, estando presente na superfície do oócito. A CD81 também tem sido associada a outros processos biológicos, contudo a sua função específica e os seus mecanismos de acção não estão elucidados. A ligação entre a CD81 e as suas proteínas interactoras fundamenta o envolvimento da CD81 numa variedade de processos celulares e funções específicas. O desenvolvimento de um sistema de Dois Híbrido em Leveduras, anteriormente realizado no nosso laboratório, mostrou que a CD81 potencialmente interage com a Proteína Percursora de Amilóide (PPA). No presente trabalho, foi realizada a análise bioinformática das proteínas interactoras da CD81. A informação obtida permitiu a construção de uma rede de interações proteína-proteína, bem como a análise de enrequecimento de Ontologia de Genes. Adicionalmente, a expressão da CD81 foi avaliada nas linhas celulares CHO, GC-1 e SH-SY5Y e em espermatozóides humanos. A sua localização subcelular foi também analisada em espermatozóides humanos e na linha de neuroblastoma SH-SY5Y. Foram ainda realizados ensaios de coimunoprecipitacão nas linhas celulares CHO e SH-SY5Y, com a tentativa de provar a intercação física entre a CD81 e a PPA. A interação funcional entre estas duas proteínas foi estudada através da análise do efeito da sobreexpressão da CD81 nos níveis de PPA. Foram também realizados estudos de colocalização entre a CD81 e algumas proteínas interactoras, nos espermatozóides humanos e na linha celular SH-SY5Y. Os interatores analisados, PPA, AKT1 e proteínas relacionadas com o citoesqueleto, foram obtidos da análise bioinformática previamente realizada. O efeito da CD81 na remodelação do citoesqueleto foi avaliado através da monitorização dos efeitos da sobre-expressão da CD81 nos níveis de actina e tubulina, bem como através da análise da colocalização entre a CD81 sobre-expressa e a F-actina. Os nossos resultados mostram que a CD81 está expressa em todas as linhas celulares testadas, providenciando a primeira evidência da presença da CD81 em espermatozóides humanos. A marcação da CD81 foi predominantemente detectada na cabeça do espermatozóde e na peça intermédia, onde colocaliza com a PPA, bem como na região pós-acrossómica. Em adição, a CD81 colocaliza com a PPA na membrana plasmática e nas projecções celulares das células SH-SY5Y, onde a sobre-expressão da CD81 influencia os níveis de PPA, efeito também observado nas células CHO. A análise de proteínas interactoras da CD81, como a AKT1 e proteínas relacionadas com o citoesqueleto, evidenciou que a CD81 está envolvida na remodelação do citoesqueleto, nomeadamente na motilidade dos espermatozóides, na migração celular e na neuritogénese. Estes resultados permitiram aprofundar o conhecimento das funções da CD81 e de alguns dos seus interactores, em espermatozóides e em células neuronais.

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40

Wonjo, Justyna. "Novel glycolipids in CD1d-mediated immunity : synthesis of new agonists of CD1d." Thesis, University of Birmingham, 2012. http://etheses.bham.ac.uk//id/eprint/3551/.

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The glycolipid α-galactosyl ceramide, α-GalCer, has been shown to stimulate the proliferation of murine spleen cells and activate the immune system. Stimulation occurs through binding of the glycolipid to the protein CD1d. Subsequent presentation of the CD1d−glycolipid complex to invariant Natural Killer T cells (iNKT cells) initiates the proliferation of a host of cytokines leading to an immune response The therapeutic potential of α-GalCer is currently being explored; however the induction of both Th1 and Th2 cytokines by this agent is likely to limit its therapeutic application. Significantly, analogues of α-GalCer have been shown to induce iNKT cell-derived cytokines more selectively through a skewed Th1-Th2 response. To date, very few alterations around the amide bond have been explored. To investigate its importance in iNKT cell stimulation, a range of α-GalCer and threitol ceramide (ThrCer) analogues has been synthesised in which the amide functionality in these two leads has been replaced with different carbonyl functional groups. These compounds have been tested for iNKT cell induction and in particular their Th1/Th2 response, which determined their therapeutic potential. Labelled derivatives of α-GalCer and ThrCer have also been designed and synthesised to find application in lipid trafficking studies.

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41

Lianga, Noel. "Cdk1 Regulates Anaphase Onset." Thesis, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/31860.

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Cdk1 is an important cell cycle regulator that, in association with different cyclin regulatory subunits, is responsible for signaling important cell cycle events in all eukaryotic cells. In budding yeast, inhibition of Cdk1 by selective deletion of cyclin subunits has been shown to prevent anaphase onset, suggesting that Cdk1 activity is critically important for triggering anaphase onset. In many eukaryotes, Cdk1 has been shown to phosphorylate subunits of the anaphase promoting complex (APC), an E3 ubiquitin ligase which directly signals anaphase onset by triggering the degradation of the anaphase inhibitor securin. It is currently unclear, however, whether the APC is the sole essential substrate of Cdk1 in anaphase onset or if Cdk1 triggers anaphase onset by phosphorylating additional proteins. Eukaryotic Cdk1 is regulated by the Wee1 family of tyrosine kinases and the Cdc25 family of phosphatases which directly oppose Wee1 activity. Wee1 phosphorylation of Cdk1 on a single tyrosine residue inhibits Cdk1 and has been shown to prevent or delay mitotic entry. In this work we sought to further elucidate the mechanism through which Cdk1 regulates anaphase onset. We showed that, in addition to regulating mitotic entry, the budding yeast Wee1 kinase and Cdc25 phosphatase (Swe1 and Mih1 respectively in S. cerevisiae) regulate anaphase onset by modulating Cdk1 activity. Activation of Swe1 delays anaphase onset and cells lacking SWE1 enter anaphase prematurely, demonstrating that Swe1 regulates anaphase onset in unperturbed cell cycles. Deletion of the CDC55 regulatory subunit of PP2A has been shown to bypass cell cycle delays due to Swe1 activation. We showed that this is due, in part, to PP2ACdc55 dephosphorylation of Cdk1 sites on the APC. We have also shown that Cdk1 directly phosphorylates separase, the protease that dissolves sister chromatid linkages upon release from inhibitory securin/separase complexes upon APC-mediated securin degradation. Similar to phosphoregulation of the APC, we showed that Cdk1 phosphorylation of separase is opposed by PP2ACdc55. Phosphoregulation of separase appears to be important for regulation of the separase substrate Slk19 which cooperates with the conserved kinesin-5 Cin8 and microtubule bundling protein Ase1 to regulate spindle elongation at the spindle midzone.

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42

Tcherkes, Anatolij [Verfasser], Dagmar [Gutachter] Riemann, Uwe [Gutachter] Lendeckel, and Dirk [Gutachter] Reinhold. "FRET-basierte Untersuchung der Kolokalisation der Aminopeptidase APN/CD13, Dipeptidyl-Peptidase/CD26 und Neprilysin/CD10 mit anderen membranständigen Molekülen / Anatolij Tcherkes ; Gutachter: Dagmar Riemann, Uwe Lendeckel, Dirk Reinhold." Halle (Saale) : Universitäts- und Landesbibliothek Sachsen-Anhalt, 2019. http://d-nb.info/1210731886/34.

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43

Gama, Lucio. "Mudanças em subgrupos de monócitos durante infecção aguda pelo vírus da imunodeficiência símia (SIV); expansão de uma população inédita de células CD14+CD16- com um fenótipo atípico CCR2-." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5146/tde-22092011-115312/.

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Monócitos podem ser classificados em três subgrupos de acordo com o nível de expressão dos marcadores CD14 e CD16. Monócitos clássicos são os mais abundantes no sangue. Eles expressam um fenótipo CD14+CD16-CCR2+, conferindo a eles a habilidade de migrar rapidamente a sítios inflamatórios, através da resposta à quimiocina CCL2 (CC chemokine ligand 2). Aqui apresentamos a identificação e caracterização de uma expansão de um novo subgrupo de monócitos durante a infecção por SIV e HIV. Essas células são indistinguíveis dos monócitos clássicos quanto à expressão de CD14 e CD16; porém não expressam CCR2 de superfície. A análise do transcriptoma de células selecionadas confirmou que elas representam uma subpopulação distinta que expressa níveis mais baixos de citocinas inflamatórias e marcadores de ativação que as CCR2+. Elas exibem fagocitose alterada e quimiotaxia deficiente em resposta a CCL2 e CCL7, além de serem refratárias à infecção por SIV e apresentarem atividade antiproliferativa. Nós as denominamos monócitos clássicos atípicos CCR2- (ACC monocytes), e acreditamos que elas têm um papel importante na patogenia da AIDS, possivelmente refletindo uma resposta anti-inflamatória contra a excessiva imunoativação observada durante a infecção por SIV e HIV. Tratamento antirretroviral leva a um declínio dessa subpopulação tanto em macacos como seres humanos, sugerindo que a replicação viral é capaz de induzir esse fenótipo atípico
Monocytes have been categorized in three main subpopulations based on CD14 and CD16 surface expression. Classical monocytes are the most abundant subset in the blood. They express a CD14+CD16-CCR2+ phenotype, which confers on them the ability to migrate to inflammatory sites by quickly responding to CC chemokine ligand 2 (CCL2) signaling. Here we identified and characterized the surge and expansion of a novel monocyte subset during SIV and HIV infection. They were undistinguishable from classical monocytes regarding CD14 and CD16 expression, but did not express surface CCR2. Transcriptome analysis of sorted cells confirmed that they represent a distinct subpopulation that expresses lower levels of inflammatory cytokines and activation markers than their CCR2+ counterparts. They exhibited impaired phagocytosis and deficient chemotaxis in response to CCL2 and CCL7, besides being refractory to SIV infection and showing antiproliferative activity. We named these cells atypical CCR2- classical (ACC) monocytes, and believe they play an important role in AIDS pathogenesis, possibly reflecting an anti-inflammatory response against the extreme immune activation observed during SIV and HIV infection. Antiretroviral therapy caused this population to decline in both macaque and human subjects, suggesting that this atypical phenotype may be induced by viral replication

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Schlegel, Magdalena [Verfasser], Katrin [Akademischer Betreuer] Schäfer, Margarete [Akademischer Betreuer] Schön, and Ralf [Akademischer Betreuer] Dressel. "Stadien-abhängiger Nachweis von CD14+- und CD16+-Zellen im humanen Herz- und Milzgewebe nach Myokardinfarkt: Eine post-mortem-Analyse / Magdalena Schlegel. Gutachter: Margarete Schön ; Ralf Dressel. Betreuer: Katrin Schäfer." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2014. http://d-nb.info/1054542163/34.

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Groyer, Emilie. "Rôle du CD31 dans l'athérothrombose." Paris 6, 2008. http://www.theses.fr/2008PA066598.

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L'athérosclérose et sa principale complication, l'athérothrombose, sont le résultat de la régulation inefficace d'une réponse inflammatoire au sein de la paroi vasculaire. Toutes les cellules impliquées dans ce processus pathologique expriment un récepteur inhibiteur, le CD31. L'objectif de mon travail de thèse a été de déterminer si le CD31 était impliqué dans l'athérosclérose. Nous avons montré que la surexpression d'une forme soluble du CD31 permettait de prévenir le développement de lésions dans un modèle murin d'athérosclérose, les souris ApoE KO. Nous avons ensuite établi que la survenue de l'athérothrombose, sous forme d'anévrisme ou de thrombus luminal, était corrélée au clivage du CD31 à la surface des lymphocytes T circulants. L'engagement de la portion de CD31 résiduel à l'aide d'un peptide nous a permis de ralentir l'évolution de l'athérosclérose et d'empêcher ses complications. En conclusion, l'ensemble de nos travaux a mis en évidence le rôle central du CD31 dans l'interface sang/vaisseaux. Le CD31 serait donc une nouvelle cible thérapeutique dans l'athérosclérose.

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46

Newton, Justin Philip. "Structure and function of CD31." Thesis, University of Oxford, 1997. https://ora.ox.ac.uk/objects/uuid:0183ecb4-a147-4772-a957-f53ae6ea367c.

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The regulated interaction of leukocyte with endothelium is of key importance during normal immune surveillance and leukocyte infiltration to sites of infection in the inflammatory response. This thesis is concerned with the structure and function of CD31 (platelet-endothelial cell adhesion molecule-1), one of the adhesion molecules implicated in these processes. Previous work has shown both in vivo and in vitro that CD31 is involved in the final step of leukocyte recruitment, transmigration across the endothelial monolayer. CD31 mediated adhesion is complex, since it is capable of mediating multiple adhesive interactions, both to itself (homophilic adhesion) and to other ligands (heterophilic adhesion). In order to study homophilic adhesion, an heterologous cell-protein assay was used in combination with recombinant chimeric CD31Fc fusion proteins, ICAM-3/CD31 chimeras and chimeras between human and murine CD31. These reagents located the homophilic binding site to the NH₂-terminal domains 1 and 2, but also define a non-binding accessory role for the membrane proximal domains. Using site-directed mutagenesis to target all of the exposed charged residues in domain 1 and a subset of charged residues in domain 2, five residues were identified, mutations in which resulted in inhibition of homophilic adhesion. These residues map to both faces of the domain 1 immunoglobulinlike fold, suggesting that each molecule of CD31 interacts with two others. A novel zipper model of homophilic adhesion involving CD31 lateral association analogous to that seen amongst cadherins is proposed on the basis of these results. Evidence for lateral association of CD31 to form dimers was obtained from biophysical, biochemical and molecular biology techniques. These show that Cd31 exists in an equilibrium between monomeric and dimeric forms both in solution as soluble recombinant protein, and at the cell surface. In solution the affinity of the interaction was calculated to lie in the range 12-14μM. A large panel of anti-CD31 monoclonal antibodies were generated and tested for their ability to effect homophilic adhesion. Inhibitory antibodies were identified, mapping throughout the extracellular domain, away from the ligand binding site. In addition possible stimulating antibodies mapping to the membrane proximal domains were also identified. This indicates that CDS 1 may be induced to undergo conformational changes which effect homophilic adhesion, and it is proposed that these conformational changes may be linked to the ability of CD31 to form laterally associated dimers. Using the reagents described above, a screen of haematopoietic cell lines identified a novel heterophilic interaction, which was shown to be mediated by the integrin αvβ3. Proteinprotein assays were used to confirm a direct physical association between CD31 and αvβ3, and to map the integrin binding site to the third immunoglobulin-like fold of CD31. The functional significance of this interaction was assessed in neutrophil transmigration assays, in which both anti-CD31 and anti-αvβ3 antibodies were found to partially inhibit neutrophil transmigration.

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47

Kimmig, Lucas [Verfasser], and Hans-Hartmut [Akademischer Betreuer] Peter. "Human CD21 Deficiency is associated with Hypogammaglobulinemia = Die menschliche CD21 Defizienz ist mit Hypogammaglobulinämie assoziert." Freiburg : Universität, 2012. http://d-nb.info/1123467293/34.

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48

Immig, Kerstin. "Immunphänotypische Charakterisierung CD11c-positiver Zellen des Gehirns im direkten Vergleich zu CD11c-positiven Zellen von Lunge, Leber und Milz." Doctoral thesis, Universitätsbibliothek Leipzig, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-200929.

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Bei der vorliegenden Arbeit handelt es sich um eine experimentell durchgeführte Charakterisierung von CD11c-positiven Zellen des Gehirns im direkten Vergleich zu CD11c-positiven Zellen aus Lunge, Leber und Milz. Mittels Konfokal- und Fluoreszenzmikroskopie wurde die Existenz von intraparenchymalen Zellen nachgewiesen, welche den Zellmarker für Dendritische Zellen CD11c exprimieren. Durch die Etablierung einer einheitlichen Isolierungsmethode von CD11c-positiven mononukleären Zellen aus dem Gehirn, Milz, Lunge und Leber, war es uns möglich, diese mittels Durchflusszytometrie, auf die Expression wichtiger Marker für mononukleäre Zellen zu untersuchen und phänotypisch miteinander zu vergleichen. Durch diese Zellanalysen zeigten wir, dass CD11c-positive Zellen des Gehirns sowohl aufgrund ihrer spezifischen CD45-Expression, als auch durch die Expression von CD11b einen Mikrogliaphänotyp aufwiesen. Dabei konnten wir beobachten, dass CD11c-positive Zellen aus dem Gehirn einzigartig in der Eigenschaft ihrer geringen Major Histocompatibility Complex (MHC)-II-Expression sind. Mit Hilfe einer transgenen Mauslinie, welche unter dem Promotor von MHC-II das grün-fluoreszierende Protein (GFP) exprimiert, konnten wir nachweisen, dass Mikroglia selbst in der Umgebung von MHC-II-positiven Zellen, kultiviert auf Schnittkulturen der Milz, ihre MHC-II-Negativität behalten. Im Vergleich dazu adaptierten sich MHC-II-positive Splenozyten, kultiviert auf Schnittkulturen vom Hippocampus, an die neue Umgebung und verringerten die Expression von MHC-II. Unsere Daten lassen also die Schlussfolgerung zu, dass sich CD11c-positive Mikroglia hinsichtlich ihrer Expression von MHC-II intrinsisch von CD11c-positiven Zellen anderer Organe unterscheiden. Ebenso scheinen auch lokale Faktoren im Gehirn dazu beizutragen, die Expression von MHC-II unter physiologischen Bedingungen wirkungsvoll zu unterdrücken.

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Baker, Bradley J. "The evolutionarily related major histocompatibility complex and CD1 : evolution of an endogenous retrovirus responsible for a polymorphism in human C4 and the biochemical characterizations of CD1A and E /." The Ohio State University, 1998. http://rave.ohiolink.edu/etdc/view?acc_num=osu148794983620512.

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50

Zevian, Shannin Christine. "Structure-function analysis of Tetraspanin CD151." Diss., University of Iowa, 2011. https://ir.uiowa.edu/etd/3022.

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The basement membrane protein laminin-332 (laminin-5) mediates both stable cell adhesion and rapid cell migration, and thus has the potential to either restrain or promote tumor cell metastasis. The major cellular receptors for laminin-332 are integrin α3β1, which mediates rapid tumor cell migration, and integrin α6β4, which often mediates stable cell attachment. Tetraspanin protein CD151 interacts directly with both α3β1 and α6β4 integrins and with other tetraspanins, thereby promoting α3β1 and α6β4 association with tetraspanin-enriched microdomains on the cell surface. To explore the possibility of selectively modulating tumor cell responses to laminin-332, we re-expressed a series of CD151 mutants in epidermoid carcinoma cells with near total, RNAi- mediated silencing of endogenous CD151. CD151's interactions with its integrin partners or its interactions with other tetraspanins were selectively disrupted by specific mutations in the CD151 large extracellular loop (EC2 domain) or in intracellular CD151 palmitoylation sites, respectively. CD151- integrin association and CD151-tetraspanin association were both important for α3β1 integrin- dependent initial adhesion and rapid migration on laminin-332. Remarkably, however, only CD151-integrin association was required for stable, α6β4 integrin-dependent cell attachment on laminin-332. In gap-filling assays, where CD151-silenced cells moved more rapidly than WT cells, again, only CD151-integrin association was required to restrict movement into the gap, suggesting that both α3β1 and α6β4 integrin must be able to associate with CD151 in order restrict group motility. In addition, we found that a QRD amino acid motif in the CD151 EC2 domain that had been thought to be crucial for CD151-integrin interaction is not essential for CD151-integrin association or for CD151's ability to promote several different integrin functions. These new data suggest potential strategies for selectively modulating migratory cell responses to laminin-332, while leaving stable cell attachment on laminin-332 intact.

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Dissertations / Theses on the topic 'CD11'

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