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van der Bruggen, T., P. T. Kok, J. A. Raaijmakers, J. W. Lammers und L. Koenderman. „Cooperation between Fc gamma receptor II and complement receptor type 3 during activation of platelet-activating factor release by cytokine-primed human eosinophils.“ Journal of Immunology 153, Nr. 6 (15.09.1994): 2729–35. http://dx.doi.org/10.4049/jimmunol.153.6.2729.
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Abstract After priming with cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, or IL-5, eosinophils are stimulated potently by opsonized particles like serum-treated zymosan (STZ), resulting in activation of the respiratory burst and production of lipid mediators, such as platelet-activating factor (PAF) and leukotriene C4 (LTC4). In the present study, the role of the opsonin receptors Fc gamma RII and CR3 during both STZ-induced activation of the respiratory burst and PAF release by human eosinophils was investigated. Inhibition studies with blocking mAbs (alpha hFc gamma RII: AT10, IV.3; alpha CR3: B2.12, 44a) showed that both Fc gamma RII and CR3 are important for STZ-induced PAF release by cytokine-primed eosinophils. In contrast, CR3 is involved in activation of the respiratory burst, whereas Fc gamma RII seems not to be important, because blocking anti-Fc gamma RII mAbs had no effect. Subsequently, experiments were performed with zymosan particles coated with IgG, iC3b, or a combination of both. IgG-coated particles poorly activated both responses in GM-CSF primed and unprimed cells. iC3b-Zymosan activated the respiratory burst as well as zymosan expressing both opsonins (IgG/iC3b-zymosan). In contrast, iC3b-zymosan induced significantly less PAF release by GM-CSF-primed eosinophils than did IgG/iC3b-zymosan, suggesting synergism between Fc gamma RII and CR3. This synergistic effect was not observed when IgG-zymosan and iC3b-zymosan were added simultaneously. Therefore, these data indicate that on human eosinophils, Fc gamma RII and CR3 act synergistically to activate PAF release, provided that their ligands are in close proximity.
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Sahlin, Herman, und Håkan Nygren. „Cytotoxicity Testing of Wound-Dressing Materials“. Alternatives to Laboratory Animals 29, Nr. 3 (Mai 2001): 269–75. http://dx.doi.org/10.1177/026119290102900319.
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A method was developed for testing the cytotoxicity of various bandage-like wound dressings and gel wound dressings. In this method, the ability of human polymor-phonuclear neutrophils (PMNs) to initiate a respiratory burst after exposure to the various wound dressings is used as a marker of cytotoxicity. Luminol-amplified chemiluminescence stimulated with opsonised zymosan or phorbol 12-myristate 13-acetate (PMA) is used to measure the degree of activation of the respiratory burst, i.e. the NADPH oxidase activity, after exposure to wound dressings. Opsonised zymosan (material from yeast cell walls) is a phagocytic stimulus that activates the NADPH oxidase by binding to Fc-receptors and complement receptors, and functions as an artificial bacterium, whereas PMA activates the NADPH oxidase by direct activation of protein kinase C. NADPH oxidase activity was inhibited by several wound dressings. The down-regulation of the respiratory burst is detrimental to the bactericial effect of PMNs, and can be used as a marker for the cytotoxicity of wound-dressing materials.
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Le Cabec, Véronique, Carine Cols und Isabelle Maridonneau-Parini. „Nonopsonic Phagocytosis of Zymosan and Mycobacterium kansasii by CR3 (CD11b/CD18) Involves Distinct Molecular Determinants and Is or Is Not Coupled with NADPH Oxidase Activation“. Infection and Immunity 68, Nr. 8 (01.08.2000): 4736–45. http://dx.doi.org/10.1128/iai.68.8.4736-4745.2000.
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ABSTRACT Complement receptor type 3 (CR3) was initially described as an opsonic receptor. Subsequently, CR3-mediated lectin-sugar recognition mechanisms have been shown to play a major role in the nonopsonic phagocytosis of several pathogens, among them Mycobacterium tuberculosis. Little is known about the binding and signal transduction mechanisms operating during nonopsonic ingestion through CR3 of different microorganisms. In the present study, we used CHO cells stably transfected with CR3 to show that CR3 was able to mediate internalization of zymosan and pathogenic mycobacteria (Mycobacterium kansasii and Mycobacterium avium) but not that of nonpathogenic species (Mycobacterium smegmatis and Mycobacterium phlei). A combination of mannan and β-glucan inhibited the phagocytosis of zymosan but had no effect on M. kansasii ingestion. Among six monoclonal antibodies (MAbs) directed against the CD11b subunit of CR3 that decreased zymosan ingestion, only three inhibited M. kansasii phagocytosis. In particular, MAbs known to block the CR3 lectin site affected only internalization of zymosan. Using U937 macrophages, we observed that zymosan ingestion through CR3 induced superoxide production measured by cytochrome c reduction and by translocation of the NADPH oxidase cytosolic component p47phox to the phagosomal membrane, whereas phagocytosis of viable or heat-killed M. kansasii did not. Furthermore, lack of superoxide anion production during phagocytosis of M. kansasii was not due to inhibition of NADPH oxidase per se or superoxide anion scavenging. Together, our results indicate that (i) nonopsonic phagocytosis of zymosan and M. kansasii by CR3 implicates different molecular mechanisms involving multiple and distinct epitopes of CD11b and (ii) CR3 may transduce different cellular responses depending on the sites mediating nonopsonic phagocytosis.
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Klebanoff, S. J., M. A. Vadas, J. M. Harlan, L. H. Sparks, J. R. Gamble, J. M. Agosti und A. M. Waltersdorph. „Stimulation of neutrophils by tumor necrosis factor.“ Journal of Immunology 136, Nr. 11 (01.06.1986): 4220–25. http://dx.doi.org/10.4049/jimmunol.136.11.4220.
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Abstract Human recombinant tumor necrosis factor (TNF) was shown to be a weak direct stimulus of the neutrophil respiratory burst and degranulation. The stimulation, as measured by iodination, H2O2 production, and lysozyme release, was considerably increased by the presence of unopsonized zymosan in the reaction mixture, an effect which was associated with the increased ingestion of the zymosan. TNF does not act as an opsonin but, rather, reacts with the neutrophil to increase its phagocytic activity. TNF-dependent phagocytosis, as measured indirectly by iodination, is inhibited by monoclonal antibodies (Mab) 60.1 and 60.3, which recognize different epitopes on the C3bi receptor/adherence-promoting surface glycoprotein of neutrophils. Other neutrophil stimulants, namely N-formyl-methionyl-leucyl-phenylalanine, the Ca2+ ionophore A23187, and phorbol myristic acetate, also increase iodination in the presence of zymosan; as with TNF, the effect of these stimulants is inhibited by Mab 60.1 and 60.3, whereas, in contrast to that of TNF, their stimulation of iodination is unaffected by an Mab directed against TNF. TNF may be a natural stimulant of neutrophils which promotes adherence to endothelial cells and to particles, leading to increased phagocytosis, respiratory burst activity, and degranulation.
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ROUIS, Mustapha, Fabienne NIGON, Thomas L. EGGERMAN, H. Bryan BREWER und M. John CHAPMAN. „Apolipoprotein E expression by human-monocyte-derived macrophages. Modulation by opsonised zymosan and cholesterol“. European Journal of Biochemistry 189, Nr. 2 (April 1990): 447–53. http://dx.doi.org/10.1111/j.1432-1033.1990.tb15509.x.
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Nair, P. K. Raveendran, Steven J. Melnick, Ziad A. Khatib, Reshma Ramachandran, Enrique A. Escalon und Cheppail Ramachandran. „Mechanism of Immune System Activation by (1,4)-α-D-glucan Isolated from Tinospora cordifolia in Macrophages.“ Blood 108, Nr. 11 (16.11.2006): 3833. http://dx.doi.org/10.1182/blood.v108.11.3833.3833.
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Abstract We have characterized and reported the immunostimulating properties of a novel polysaccharide - (1,4)-α-D-glucan (RR1)- isolated from the medicinal plant Tinospora cordifolia [23]. This novel glucan is water soluble and having (1, 4)-α-D-glycosidic linkages in the main chain and (1, 6)-α-D-glycosidic linked side chains at an interval of 6, 7 glucose units. The signaling mechanism of the novel (1,4)-a-D-glucan (RR1) was investigated in macrophages to evaluate its immunostimulating properties. When RAW264.7 macrophages were incubated with RR1 at 4°C, the novel glucan inhibited the phagocytosis of unopsonized zymosan A bioparticles in a dose-dependent manner. RR1 also inhibited the binding and internalization of opsonized zymosan A bioparticles, although at a lower level than laminarin. Incubation of macrophages with anti-CD11b mAb followed by RR1 failed to show any inhibitory effect on RR1-induced TNF-α synthesis confirming that complement receptor 3 (CR3) is not involved in the opsonic binding and internalization of RR1 in macrophages unlike zymosan A. The anti-CD11b mAb has significant inhibitory effect on the zymosan A-induced tumor necrosis factor (TNF)-α synthesis. RR1 induced TNF-α synthesis in macrophages in a dose-dependent manner which can be completely inhibited by the NF-κB inhibitor caffeic acid phenethyl ester (CAPE) or curcumin. RR1 activated NF-κB in a time- and dose-dependent manner and this modulation of nuclear NF-κB activity is associated with the degradation of I-κB a thus facilitating the translocation of NF-κB into the nucleus. RR1-induced NF-κB activity peaks at 8 h of RR1 stimulation while I-κB a degradation occurred within 1 h of stimulation. RR1-induced NF-κB activation occurred through TLR6 signaling as evidenced by the synthesis of IL-8 in TLR6-transfected HEK293 cells. These results show that the novel (1,4)-α-D glucan from Tinospora cordifolia activates the immune system through the activation of macrophages that occurs through TLR6 signaling, NF-κB translocation and cytokine production. (Supported by Miami Children’s Hospital Foundation research funds).
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Melnick, D. A., W. M. Nauseef, S. D. Markowitz, J. P. Gardner und H. L. Malech. „Biochemical analysis and subcellular localization of a neutrophil-specific antigen, PMN-7, involved in the respiratory burst.“ Journal of Immunology 134, Nr. 5 (01.05.1985): 3346–55. http://dx.doi.org/10.4049/jimmunol.134.5.3346.
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Abstract The adherence of serum-opsonized yeast to neutrophils results in phagocytosis of these particulate stimuli and activation of the respiratory burst. Both events are mediated or modulated in part by the surface receptors for IgG and complement. The link between the binding of complex particulate stimuli to the cell surface, and the triggering of these neutrophil functions, is not completely understood. We have previously described an anti-human neutrophil, murine monoclonal antibody PMN7C3, which specifically inhibits the respiratory burst of neutrophils stimulated with serum-opsonized yeast. In the present study, we show that the antigen recognized by PMN7C3 (PMN7 antigen) is present on a number of neutrophil proteins, including the recently described group of related leukocyte membrane glycoproteins CR3, LFA-1, and p150,95. The PMN-7 antigen differs from other antigens associated with the C3bi receptor complex (MAC 1, MO 1, OKM1, OKM10) in that it is present only on neutrophils among peripheral blood cells. Furthermore, the binding of PMN7C3 to the neutrophil surface inhibits the activation of the respiratory burst by serum opsonized zymosan without affecting phagocytosis of these particulate stimuli. The cross-linking of cell surface PMN7 antigen by multivalent antibody is associated with the capping and internalization of antigen-antibody complexes, and appears to be necessary for the expression of maximum inhibition of opsonized zymosan-triggered respiratory burst activity. PMN7C3 also binds to a group of granule-associated proteins biochemically distinct from CR3, LFA-1, and p150,95. These granule-associated proteins containing PMN7 antigen can be mobilized to the cell surface with secretion. PMN7 antigen-bearing proteins may play a role in modulating the activation of the respiratory burst associated with phagocytosis of serum-opsonize zymosan.
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Diniz, S. N., R. Nomizo, P. S. Cisalpino, M. M. Teixeira, G. D. Brown, A. Mantovani, S. Gordon, L. F. L. Reis und A. A. M. Dias. „PTX3 function as an opsonin for the dectin-1-dependent internalization of zymosan by macrophages“. Journal of Leukocyte Biology 75, Nr. 4 (14.01.2004): 649–56. http://dx.doi.org/10.1189/jlb.0803371.
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Worku, Mulumebet, Max J. Paape, Andrea Di Carlo, Marcus E. Kehrli und Warren W. Marquardt. „Complement component C3b and immunoglobulin Fc receptors on neutrophils from calves with leukocyte adhesion deficiency“. American Journal of Veterinary Research 56, Nr. 4 (01.04.1995): 435–39. http://dx.doi.org/10.2460/ajvr.1995.56.04.435.
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SUMMARY Receptors for opsonins, such as complement component C3b (CR1) and immunoglobulins, Fc receptors, interact with adhesion glycoproteins in mediating immune functions. Defects in expression of the adhesion glycoproteins CD11/CD18 results in severely hampered in vitro and in vivo adherence- related functions of leukocytes. Little is known regarding the effect of leukocyte adhesion deficiency (lad) on ligand binding and receptor expression. We investigated the binding and expression of CR1 and Fc receptors by bovine neutrophils isolated from dairy calves suffering from lad, compared with clinically normal (hereafter referred to as normal) age-matched calves. Neutrophils were also assayed for endogenously bound IgG and IgM and for exogenous binding of C3b, IgG1, IgG2, IgM, and aggregated IgG (aIgG), using flow cytometry. Luminol-enhanced chemiluminescence (cl) production in response to IgG2 opsonized zymosan was studied, and specific inhibition of cl was used to determine the specificity of IgG2 binding. Activation of protein kinase C with phorbol myristate acetate was used to determine the effect of cellular activation on expression of CR1. A greater percentage of neutrophils from normal calves bound C3b than did neutrophils from lad- affected calves. Receptor expression was similar. Activation with phorbol myristate acetate resulted in increased expression of CR1 on neutrophils from normal and lad-affected calves, but expression was almost twofold greater on neutrophils from normal calves. There was no difference between lad-affected and normal calves in percentage of neutrophils that bound endogenous IgG and IgM. A greater percentage of neutrophils from normal calves bound exogenous IgM than did neutrophils from lad-affected calves. Receptor expression for aIgG was greater on neutrophils from lad-affected calves than on those from normal calves. Luminol-enhanced cl of neutrophils in response to IgG2 opsonized zymosan was not different between lad-affected and normal calves. Results indicate increased binding and expression of Fc receptors for aIgG and decreased binding and expression for C3b and IgM on neutrophils from calves with lad. Leukocyte adhesion deficiency may be compounded by added defects in the expression and binding of receptors for opsonins, such as C3b and IgM.
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Bartoskova, A., P. Ondrackova, L. Leva, R. Vitasek, R. Novotny, M. Janosovska und M. Faldyna. „The effects of in vitro exposure to progesterone and estradiol-17β on the activity of canine neutrophils“. Veterinární Medicína 59, No. 4 (17.06.2014): 202–9. http://dx.doi.org/10.17221/7481-vetmed.
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To date, only limited information about the influence of ovarian hormones on canine immune system cells has been available. The study investigated the in vitro influence of progesterone and estradiol-17β on the activity of canine neutrophils. Treatment of cells by both hormones led to a significant decrease in phagocytosis-induced oxidative burst as detected using luminometry after stimulation with opsonised zymosan. The increase in oxidative burst, not connected with phagocytosis, was recorded after stimulation with a soluble stimulator. Using flow cytometry, the tendency of both hormones to decrease the production of reactive oxygen species associated with phagocytosis of Escherichia coli was also evident, although not significant. Suppression of canine neutrophil activity is not connected with pathogen recognition capabilities, since the expression of Toll-like receptor 4 was unaffected. This study reveals that both hormones have a suppressive effect on the activity of canine neutrophils and thus might contribute to the aetiology of pyometra.
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BASSØE, CARL-FREDRIK, und ROBERT BJERKNES. „THE EFFECT OF SERUM OPSONINS ON THE PHAGOCYTOSIS OF STAPHYLOCOCCUS AUREUS AND ZYMOSAN PARTICLES, MEASURED BY FLOW CYTOMETRY“. Acta Pathologica Microbiologica Scandinavica Series C: Immunology 92C, Nr. 1-6 (15.08.2009): 51–58. http://dx.doi.org/10.1111/j.1699-0463.1984.tb00051.x.
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Watson, G. L., R. F. Slocombe, N. E. Robinson und S. D. Sleight. „Definition of chemiluminescence and superoxide production responses of bovine neutrophils to selected soluble and particulate stimulants, and comparisons with the responses to Pasteurella haemolytica“. American Journal of Veterinary Research 56, Nr. 8 (01.08.1995): 1045–54. http://dx.doi.org/10.2460/ajvr.1995.56.08.1045.
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SUMMARY We defined methods for use of luminol-dependent chemiluminescence (ldcl) and superoxide anion (O2-) production as parameters of the oxidative metabolism of neutrophils isolated from 1.5- to 5-week-old neonatal calves. We determined how variations in blood sample handling, agonist preparation, individual variability, and age of calves influenced the ldcl and O2- responses to certain agonists, and defined concentrations of soluble and particulate agonists that maximally stimulated the oxidative metabolism of bovine neutrophils. Oxidative responses, particularly ldcl, were characterized by marked day-to-day variability, differed greatly within and between calves, were partially age-dependent, and were partially dependent on the individual agonist. Superoxide anion production had substantially less variability. We compared the in vitro oxidative (ldcl and O2-) responses of neutrophils isolated from neonatal calves stimulated by defined concentrations of the agonists–latex, phorbol myristate acetate, calcium ionophore, and opsonized zymosan–with responses to formylated oligopeptides and zymosan-activated serum, and to live, dead, live opsonized, and dead opsonized Pasteurella haemolytica organisms. Opsonization of particulates, pathogenic or nonpathogenic, enhanced the ldcl and O2- responses of stimulated neutrophils although P haemolytica was a less potent stimulant of oxidative functions than were nonbiological agonists. We conclude that the generation of reactive oxygen species by bovine neutrophils in response to P haemolytica is highly dependent on the presence of opsonins and is greatly enhanced in live vs killed bacteria. Furthermore, the in vitro generation of reactive oxygen species, including O2- by stimulated neutrophils, may be of biologic importance if similar events occur in vivo, and could have a major role in the pathogenesis of the acute lung injury associated with pneumonic pasteurellosis.
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Peterson, Erica A., Jonathan H. Foley, Michael J. Krisinger und Edward Conway. „Plasmin Cleaves Complement iC3b, Preventing CR3/4 Mediated Phagocytosis By Macrophages“. Blood 122, Nr. 21 (15.11.2013): 1105. http://dx.doi.org/10.1182/blood.v122.21.1105.1105.
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Abstract Introduction The plasmin(ogen) and complement systems are activated at sites of tissue injury and are involved in hemostasis, wound healing, inflammation and immune surveillance. Although the mechanisms are poorly understood, dysregulation of these systems underlie the pathogenesis and progression of inflammatory and vascular diseases. We aimed to characterize the relevant molecular interactions between the plasmin(ogen) and complement pathways. The three complement pathways converge with formation of C3-convertases that cleave C3 into C3a and C3b. C3a is liberated as an anaphylatoxin while C3b participates in further formation of the C3 and C5 convertases, thereby amplifying complement activation. To dampen the system, negative regulatory mechanisms exist. C3b is degraded to iC3b by the factor I (FI)/FH complex, which in turn is degraded to C3dg by the FI/complement receptor 1 (CR1) complex. iC3b and C3dg induce cellular responses by binding to complement receptors CR3 / CR4 / CR2, and CR2, respectively. Interactions of iC3b with CR3 or CR4 induce phagocytosis by macrophages, and binding of iC3b or C3dg to CR2 promotes B-cell responses. Recent studies show that plasmin proteolyses C3b and iC3b. We further characterized the plasmin cleavage sites in iC3b and evaluated the functional consequences in vitro. Methods and Results Plasmin cleavage of iC3b was examined over a range of concentrations and times. Plasmin (50 nM) generated a 40 kDa iC3b cleavage fragment (946TLD – PSR1303) which was notable for containing both C3dg (1002HLI – PSR1303) and the C3 thioester domain, necessary for opsonic binding to surfaces. We tested the relevance of this cleavage in phagocytosis assays using immunofluorescence and flow cytometry (Figure 1). C3b bound to the surface of fluorescent (Alexa 488) zymosan particles (C3b-zym), was treated with FI/FH to generate iC3b-zym, and subsequently incubated with FI/CR1 or plasmin to yield C3dg-zym or 946TLD – PSR1303-zym, respectively. Western blots confirmed that plasmin generated 946TLD – PSR1303 from iC3b-zym. The C3 fragment-zymosan species (C3b-zym, iC3b-zym, C3dg-zym and 946TLD – PSR1303-zym) were each incubated with macrophages (PMA-differentiated THP-1 cells) for 90 minutes. Cells were washed, stained and fixed for immunofluorescence, or suspended for flow cytometry. Figure 1, panel A shows macrophages stained with CellMask (red, cell membrane) and DAPI (blue, nucleus). Fluorescent zymosan is seen in green. No phagocytosis was detected with zymosan lacking C3 (zym alone), but there was a small amount with C3b-zym. In contrast, iC3b-zym was highly effective in inducing phagocytosis by most macrophages. This effect of iC3b-zym was abolished with FI/CR1 or plasmin, i.e. little phagocytosis was detected with C3dg-zym or 946TLD – PSR1303-zym. Flow cytometry-based quantitative analyses confirmed the preceding findings (Figure 1, panel B), with a similar pattern of phagocytosis induced by the zymosan-bound fragments. No phagocytosis was detected with zymosan lacking C3. Phagocytosis of C3b-zym and iC3b-zym was 7±2% and 17±1% of cells, respectively. C3dg-zym and 946TLD – PSR1303-zym induced phagocytosis was <5%. We also evaluated the role of the complement receptors in mediating the effect of the C3b/iC3b fragments using CR3/4 and CR1 blocking antibodies. These confirmed that phagocytosis of iC3b-zym and C3b-zym is mediated by CR3/4 and CR1, respectively. Conclusions Plasmin cleaves iC3b to form a redundant complement regulatory pathway with the FI/CR1 complex, but which notably does not require a cellular cofactor. Further studies will delineate the role of this and other plasmin-generated complement fragments in modulating innate immune and inflammatory responses. Disclosures: No relevant conflicts of interest to declare.
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Dent, Gordon, Mark A. Giembycz, Klaus F. Rabe und Peter J. Barnes. „Inhibition of eosinophil cyclic nucleotide PDE activity and opsonised zymosan-stimulated respiratory burst by ‘type IV’-selective PDE inhibitors“. British Journal of Pharmacology 103, Nr. 2 (Juni 1991): 1339–46. http://dx.doi.org/10.1111/j.1476-5381.1991.tb09790.x.
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Schnur, R. A., und S. L. Newman. „The respiratory burst response to Histoplasma capsulatum by human neutrophils. Evidence for intracellular trapping of superoxide anion.“ Journal of Immunology 144, Nr. 12 (15.06.1990): 4765–72. http://dx.doi.org/10.4049/jimmunol.144.12.4765.
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Abstract Human neutrophils (PMN) have received little attention as to the role they play in host defense against Histoplasma capsulatum (Hc). We have characterized the binding and phagocytosis of Hc yeasts by human PMN and quantified the PMN respiratory burst in response to this organism. mAb specific for CD11a, CD11b, and CD11c all partially blocked the attachment of unopsonized yeasts to PMN; a mAb to CD18 inhibited attachment by greater than 90%. Thus, human PMN recognize and bind Hc yeasts via CD18 adhesion receptors as has been found for human cultured macrophages and alveolar macrophages. Unopsonized yeasts were phagocytosed by PMN, but phagocytosis was increased markedly by heat-labile and heat-stable serum opsonins. These opsonins promoted enhanced phagocytosis of yeasts by increasing the attachment of Hc yeasts to the PMN membrane. Phagocytosis of viable or heat-killed Hc yeasts by PMN did not induce the secretion of superoxide anion (O2-) as quantified by the reduction of cytochrome c. O2- was not detected when yeasts were opsonized in normal serum or immune serum, or at a ratio of yeasts to PMN of up to a 100:1. However, phagocytosis of opsonized yeasts by PMN did not prevent them from subsequently releasing O2- after further incubation with opsonized zymosan or PMA. Opsonized Hc yeasts clearly stimulated the PMN respiratory burst as quantified by intracellular reduction of nitroblue tetrazolium, reduction of cytochrome c in the presence of cytochalasin D, oxygen consumption, luminol-enhanced and nonenhanced chemiluminescence, and H2O2 production. These data suggest that phagocytosis of Hc yeasts by PMN is associated with intracellular entrapment of O2- that is not detectable by reduction of extracellular cytochrome c.
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Czop, J. K., M. F. Gurish und J. L. Kadish. „Production and isolation of rabbit anti-idiotypic antibodies directed against the human monocyte receptor for yeast beta-glucans.“ Journal of Immunology 145, Nr. 3 (01.08.1990): 995–1001. http://dx.doi.org/10.4049/jimmunol.145.3.995.
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Abstract beta-Glucan receptors are present on mammalian phagocytic cells and provide an important physiologic mechanism for opsonin-independent clearance of yeasts and fungi. To prepare an immunologic probe to human monocyte beta-glucan receptors, an approach was taken that focused on the ligand specificity of the receptors as expressed by an anti-Id. The algal beta-glucan laminarin was chemically coupled to protein carriers to prepare an immunogenic beta-glucan. Three mouse IgG2a mAb were raised against laminarin, and one, mAb OEA10, exhibited specificity for the soluble unit ligand yeast heptaglucoside and the ligands present on zymosan and glucan particles that are recognized by monocyte beta-glucan receptors. These findings prompted usage of mAb OEA10 as immunogen for the preparation of an anti-Id. The resulting rabbit antiserum was subjected to sequential immunoaffinity chromatography to purify anti-idiotypic antibodies. The final product contained only IgG by SDS-PAGE and was shown to be specific by its selectively blocking binding of 125I-mAb OEA10 to laminarin. Pretreatment of adherent monocytes with 0.4 micrograms/ml of the anti-Id reduced the numbers of monocytes ingesting zymosan and glucan particles by 64 and 43%, respectively, whereas ingestion of IgG-coated SRBC was unaffected by as much as 16 micrograms/ml of the anti-Id. Incubation of adherent monocytes with increasing amounts of 125I-anti-Id in the absence and presence of 40-fold molar excess unlabeled anti-Id revealed dose-dependent specific binding, which approached plateau levels with 1 microgram/ml of labeled anti-Id. Thus, the anti-Id binds to monocytes and displays functional characteristics of soluble beta-glucan ligands, indicating that some of the anti-idiotypic antibodies recognize epitopes within monocyte beta-glucan receptors.
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Jiang, W. G., M. C. A. Puntis und M. B. Hallett. „U937 cells stimulated with opsonised zymozan particles provide a convenient laboratory source of tumour necrosis factor α“. Journal of Immunological Methods 152, Nr. 2 (August 1992): 201–7. http://dx.doi.org/10.1016/0022-1759(92)90141-f.
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Fuentes, Ana-Lucía, Leonard Millis, Jacqueline Vapenik und Lynette Sigola. „Lipopolysaccharide-mediated enhancement of zymosan phagocytosis by RAW 264.7 macrophages is independent of opsonins, laminarin, mannan, and complement receptor 3“. Journal of Surgical Research 189, Nr. 2 (Juni 2014): 304–12. http://dx.doi.org/10.1016/j.jss.2014.03.024.
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Krumrych, Wiesław, und Janusz Danek. „Chemiluminescence of Peripheral Blood Neutrophils in Mares with Endometritis“. Bulletin of the Veterinary Institute in Pulawy 56, Nr. 1 (01.03.2012): 51–56. http://dx.doi.org/10.2478/v10213-012-0010-8.
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Abstract The aim of the study was to evaluate the oxygen metabolism of neutrophils in peripheral blood of mares in relation to intensity of endometrium inflammations. The study involved 36 half-breed mares, aged 4-22 years, showing fertility disturbances. In 26 mares neutrophils were found in uteral smears, which indicated endometritis (15 - moderate inflammation and 11 - severe inflammation). In the rest mares, cytological examination excluded inflammation. Blood samples were evaluated in terms of neutrophils chemiluminescence without stimulation (CL-WS) and with stimulation by opsonised zymosan (CL-OZ). The study demonstrated (only in case of CL-WS) an increase in chemiluminescence of cells in mares with a severe inflammation of the endometrium. The increased chemiluminescence activity was accompanied by a decrease in activation index (OZ/WS) of neutrophils, suggesting some imbalance between production and elimination of reactive oxygen species (ROS). The correlation analysis demonstrated a statistically significant relation between the intensity of the uterus inflammation, which was verified by cytological examination and CL-WS of peripheral blood neutrophils, as well as their activation index. The obtained results suggest that activated neutrophils are an important source of ROS which can play a role in the pathogenesis of endometritis in mares.
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Karlsson, Sofia, Eewa Nånberg, Christina Fjaeraa und Jonny Wijkander. „Ellagic acid inhibits lipopolysaccharide-induced expression of enzymes involved in the synthesis of prostaglandin E2 in human monocytes“. British Journal of Nutrition 103, Nr. 8 (01.12.2009): 1102–9. http://dx.doi.org/10.1017/s0007114509992935.
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Ellagic acid, a natural polyphenol found in certain fruits, nuts and vegetables, has in recent years been the subject of intense research within the fields of cancer and inflammation. Pain, fever and swelling, all typical symptoms of inflammation, are ascribed to elevated levels of PGE2. In the present study, we have investigated the effects of ellagic acid on PGE2 release and on prostaglandin-synthesising enzymes in human monocytes. Ellagic acid was found to inhibit Ca ionophore A23187-, phorbol myristate acetate- and opsonised zymosan-induced release of PGE2 from monocytes pre-treated with the inflammatory agent lipopolysaccharide. Ellagic acid suppressed the lipopolysaccharide-induced increase in protein expression of cyclo-oxygenase-2 (COX-2), microsomal PGE synthase-1 (mPGEs-1) and cytosolic phospholipase A2α (cPLA2α), while it had no effect on the constitutively expressed COX-1 protein. Ellagic acid had no apparent inhibitory effect on these enzymes when the activities were determined in cell-free assays. We conclude that the inhibitory effect of ellagic acid on PGE2 release from monocytes is due to a suppressed expression of COX-2, mPGEs-1 and cPLA2α, rather than a direct effect on the activities of these enzymes.
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SUPER, M., R. J. LEVINSKY und M. W. TURNER. „The level of mannan-binding protein regulates the binding of complement-derived opsonins to mannan and zymosan at low serum concentrations“. Clinical & Experimental Immunology 79, Nr. 2 (Februar 1990): 144–50. http://dx.doi.org/10.1111/j.1365-2249.1990.tb05170.x.
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Stokes, Richard W., Lisa M. Thorson und David P. Speert. „Nonopsonic and Opsonic Association of Mycobacterium tuberculosis with Resident Alveolar Macrophages Is Inefficient“. Journal of Immunology 160, Nr. 11 (01.06.1998): 5514–21. http://dx.doi.org/10.4049/jimmunol.160.11.5514.
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Abstract The association of Mycobacterium tuberculosis with alveolar macrophages (Mφ) in a serum-free environment is a crucial first step in the pathogenesis of this facultative intracellular pathogen. We present data demonstrating that freshly explanted alveolar Mφ do not efficiently bind M. tuberculosis in a serum-free system, although a small subpopulation of these Mφ (10–15%) can bind mycobacteria. In contrast, almost 100% of a peritoneal Mφ population bind mycobacteria under the same conditions. The poor binding of mycobacteria by alveolar Mφ does not reflect a general inability to associate with particles; binding and ingestion of latex beads and zymosan particles were comparable with that seen with peritoneal Mφ. Resident alveolar Mφ did not efficiently bind mycobacteria in the presence of serum and expressed poorly several Mφ surface receptors, including CR3. Furthermore, we demonstrate that bovine surfactant protein A does not enhance the association of M. tuberculosis with alveolar Mφ. Differentiation of alveolar Mφ in vitro resulted in increased expression of Mφ surface receptors and an increased capacity to bind mycobacteria in the presence and absence of serum. Evidence is presented that opsonic binding of M. tuberculosis by differentiated alveolar Mφ is mediated by complement and CR3, and that the poor binding by resident alveolar Mφ is due to their poor expression of CR3. The receptor mediating nonopsonic binding of M. tuberculosis to differentiated alveolar Mφ was not unequivocally identified in this study, but could also be CR3.
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Das, Hemen, Golla Ramalinga Reddy, Tukaram More und Vineet Kumar Singh. „In Vitro Effects of Certain Membrane-acting Agents on Superoxide and Hydrogen Peroxide Production, Protein Synthesis and Membrane ATPase Activity in Buffalo PMN Cells“. Alternatives to Laboratory Animals 35, Nr. 4 (August 2007): 397–404. http://dx.doi.org/10.1177/026119290703500404.
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Polymorphonuclear (PMN) cells play a key role in innate immunity, due to their ability to produce reactive oxidants such as superoxide (O2–) and hydrogen peroxide (H2O2), and to release antimicrobial proteins and peptides stored in their lysosomal granules. In the present study, the effects of the activation of buffalo PMN cells with various membrane-acting agents were evaluated in terms of O2– and H2O2 production, the activities of membrane ATPases, and protein synthesis. Studies involving the incorporation of 35S-methionine revealed significant protein-synthesising ability in resting PMN cells and in cells treated with lipopolysaccharide (LPS), as well as with opsonised zymosan (OZ). Protein synthesis, as judged by fluorography of the cytosolic fraction, showed more than 12 bands, whilst the cytoskeletal fraction showed 2–3 bands. PMN activation with concanavalin A (ConA), digitonin and sodium nitroprusside (SNP) resulted in increased O2– and H2O2 production. However, in the presence of anti-inflammatory agents such as indomethacin and cortisol, the production of O2– and H2O2 by these cells was found to decline. Studies pertaining to membrane ATPases revealed that verapamil hydrochloride (VpHCl) significantly increased total ATPase and Na+K+ATPase activity. ConA treatment yielded only a moderate level of activity. Similarly, digitonin up to 24μM also caused a significant increase in ATPase activity. Our observations indicate that these membrane-acting agents influenced oxygen-dependent and oxygen-independent microbicidal mechanisms in buffalo PMN cells.
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Coxon, Patricia Y., James T. Summersgill, Julio A. Ramirez und Richard D. Miller. „Signal Transduction during Legionella pneumophila Entry into Human Monocytes“. Infection and Immunity 66, Nr. 6 (01.06.1998): 2905–13. http://dx.doi.org/10.1128/iai.66.6.2905-2913.1998.
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ABSTRACT Legionella pneumophila causes Legionnaires’ disease by replication in alveolar macrophages and monocytes. The bacteria are internalized most efficiently by opsonin-dependent, CR3-mediated phagocytosis. This investigation focused on determining the role of actin polymerization and phosphorylation signals in this uptake mechanism. Uptake inhibition assays and confocal microscopic analysis indicated that entry of L. pneumophila activated tyrosine kinase (TK) and protein kinase C (PKC) and induced actin polymerization at the site of bacterial entry. Upon L. pneumophila entry, six major cellular proteins (75, 71, 59, 56, 53, and 52 kDa) were TK phosphorylated in soluble fractions of monocytes, and three of these proteins (52, 53, and 56 kDa) were consistently found in insoluble (i.e., cytoskeletal) fractions of monocytes as well. Tyrosine phosphorylation was suppressed when cells were pretreated with the kinase inhibitor genistein, tyrphostin, or staurosporine. A similar tyrosine-phosphorylated protein pattern was observed with CR3-mediated entry of avirulent L. pneumophila, Escherichia coli, or zymosan into monocytes. This study has shown that PKC and TK signals which activate actin polymerization during the process of phagocytosis are induced upon L. pneumophila entry. In addition, CR3 receptor-mediated phagocytosis into monocytes may involve tyrosine phosphorylation of similar proteins, regardless of the particle being phagocytosed. Therefore, the tyrosine-induced phosphorylation observed during opsonized L. pneumophilaentry is not a virulence-associated event.
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Koenderman, L., A. T. Tool, D. Roos und A. J. Verhoeven. „Priming of the respiratory burst in human eosinophils is accompanied by changes in signal transduction.“ Journal of Immunology 145, Nr. 11 (01.12.1990): 3883–88. http://dx.doi.org/10.4049/jimmunol.145.11.3883.
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Abstract Addition of platelet-activating factor (PAF) to human eosinophils leads to the modulation of eosinophil responses. The respiratory burst, induced by opsonized particles, consists of an initiation and a propagation phase and is greatly enhanced ("primed") after pretreatment with PAF. This priming event induces the following changes in signal transduction between the opsonin receptors (in particular the CR3 receptor) and activation of the respiratory burst: 1) an enhanced activation of protein kinase C (PK-C): the initiation of the respiratory burst in untreated eosinophils is not sensitive to PK-C inhibition (via staurosporine) and is not accompanied by accumulation of diglycerides and changes in [Ca2+]i. After pretreatment with PAF, the initiation of the response is partly sensitive to inhibition of PK-C (via staurosporine) and is accompanied by accumulation of diglycerides and a fast and sustained increase in [Ca2+]i; and 2) an enhancement of a PK-C-independent initiation of the respiratory burst. The propagation phase in both primed and unprimed cells is sensitive for inhibition by staurosporine. Our results indicate that in eosinophils the phospholipase(s) responsible for the accumulation of the diglycerides and changes in [Ca2+]i during the initiation phase of the serum-treated zymosan response seem(s) to become associated with the signal transduction route only after priming with PAF. This results in the occurrence of two signal transduction routes that can act independently of each other.
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Markiewicz, H., W. Krumrych und M. Gehrke. „The effect of supportive E. coli mastitis treatment on PMN chemiluminescence and subpopulations of T lymphocytes“. Polish Journal of Veterinary Sciences 16, Nr. 4 (01.12.2013): 671–77. http://dx.doi.org/10.2478/pjvs-2013-0095.
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Abstract The aim of this field study was to assess the impact of a single i.m. injection of lysozyme dimer and flunixin meglumine in combination with intramammary and systemic antibiotic on chemiluminescence of PMN (polymorphonuclear leucocytes) and subpopulations of lymphocyte T in blood of cows with E. coli mastitis. Examinations were performed on 30 dairy cows affected with naturally occurring acute form of E. coli mastitis. Cows were randomly divided into three groups according to the method of treatment. The first group was treated with approved intramammary antibiotic product, the same antibiotic in i.m. injection and one injection of flunixin meglumine on the first day of therapy. Next group was treated with the same antibiotic and additionally one injection of lysozyme dimer on the first day of therapy. The third one was treated only with an antibiotic and served as a control group. Blood samples were taken before treatment and on days 3 and 7. In samples haematology indices were determined, spontaneous and opsonised zymosan stimulated CL and PMA measurements were performed and the subpopulations of T lymphocyte (CD2+, CD4+, CD8+) were assayed in whole blood. There was no effect of the applied supportive treatment on the value of morphological blood indices. A significant influence of the time of sample collection on the level of CL and dynamics of lymphocytes T subpopulation was demonstrated. A single injection of flunixin meglumine or lysozyme dimer on the day of the beginning of treatment of E. coli mastitis, does not affect the level of neutrophil chemiluminescence and the percentage of T lymphocytes in the blood of mastitic cows in the analysed period of time.
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Kruskal, B. A., K. Sastry, A. B. Warner, C. E. Mathieu und R. A. Ezekowitz. „Phagocytic chimeric receptors require both transmembrane and cytoplasmic domains from the mannose receptor.“ Journal of Experimental Medicine 176, Nr. 6 (01.12.1992): 1673–80. http://dx.doi.org/10.1084/jem.176.6.1673.
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Phagocytosis has traditionally been viewed as a specialized function of myeloid and monocytic cells. The mannose receptor (MR) is an opsonin-independent phagocytic receptor expressed on tissue macrophages. When human MR cDNA is transfected into Cos cells, these usually non-phagocytic cells express cell surface MR and bind and ingest MR ligands such as zymosan, yeast, and Pneumocystis carinii. Expression of cDNA for Fc gamma RI (CD64), the high-affinity Fc receptor, in Cos cells confers binding but barely detectable phagocytosis of antibody-opsonized erythrocytes (EA). We report here that chimeric receptors containing the ligand-binding ectodomain of the Fc receptor and the transmembrane and cytoplasmic domains of the MR ingest bound EA very efficiently, whereas chimeras with the Fc receptor ecto- and transmembrane domains and the MR tail, or the Fc receptor ecto- and cytoplasmic domains and the MR transmembrane region, are significantly less phagocytic. All of the chimeric receptors bind ligand with equal avidity, but gain of functional phagocytosis is only conferred by the MR transmembrane and cytoplasmic domains. Endocytosis of monomeric immunoglobulin G by chimeric receptors demonstrates a similar pattern, with optimal uptake by the chimera containing both tail and transmembrane regions from the MR. The chimeric receptors with only the transmembrane or the cytoplasmic domain contributed by the MR were less efficient. Site-directed mutagenesis of the single tyrosine residue in the cytoplasmic tail (which is present in a motif homologous to an endocytosis consensus motif in the LDL receptor cytoplasmic tail [Chen, W.-J., J. L. Goldstein, and M. S. Brown. 1990. J. Biol. Chem. 265:3116]) reduces the efficiency of phagocytosis and endocytosis to a similar extent.
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Sun, Haimin, Xinlei Chen, Jiang Zhu, Zhu Chen und Saijuan Chen. „Palladin Regulates Receptor Clustering and Actin Dynamics in Phagocytosis“. Blood 128, Nr. 22 (02.12.2016): 2505. http://dx.doi.org/10.1182/blood.v128.22.2505.2505.
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Abstract BACKGROUND: Palladin is an actin microfilament associated protein, which together with myotilin and myopalladin form a novel cytoskeletal IgC2 domain protein family. However, little is known about the function of Palladin in myeloid cells. Here, we focus on the function of Palladin in phagocytosis. METHODS: We used ATRA induced differentiated NB4 cells as neutrophil-like cells, and lenti-viruses were used to build cell lines with palladin or ocrl knockdown and VAMP3-mcherry overexpression. Flow cytometry and immunofluorescence were used to detect the phagocytic ability under conditional opsonins, and the role of palladin knockdown on phagocytic events and F-actin dynamics were observed. CD32 antibodies followed with fluorescent secondary antibody were used as immune complex to stimulate FcγR clustering. We performed the mass spectrometry analysis on the immunoprecipitation (IP) lysate of differentiated NB4 cells, and the protein-protein interactions were confirmed by co-IP experiments; the colocalization and recruitment of different proteins or moleculars were observed under microscopy. RESULTS: Palladin was up-regulated during ATRA induced differentiation of several AML cell lines, as well as primary mouse bone marrow cells, and its upregulation correlated with increased phagocytic ability. Palladin defective cells showed impaired serum-mediated, IgG- or complement-mediated phagocytosis. The binding ability was measured at 4℃. After 1 hour incubation, ~17% of control cells bound with beads, whereas only ~7% palladin knockdown cells bound with beads, which suggests that Palladin regulated the particle binding. Using serum-opsonized zymosan-FITC as phagocytic targets, we found early phagosome formation, including the pseudopod extension and phagosome closure, was impaired in palladin knockdown cells. However, no significant effect was observed on the recruitment of VAMP3-mcherry, EEA1, Rab7 and LAMP1, so Palladin may not affect the focal exocytosis and phagosome maturation. The binding defect in Palladin-deficient cells was not attributable to difference in the cell surface expression of Fcγ receptor (FcγR). However, the FcγR clustering was much lower in Palladin-deficient cells. We explored how Palladin influenced the FcγR clustering, and our results showed that Palladin could regulate actin cytoskeleton dynamics and c-Src kinase activation, which resulted in the FcγR clustering. We also found that in palladin knockdown cells the actin remodeling was detained at both pseudopod extension stage and actin deploymerization stage. The Rac1 were accumulated in higher amount in the blocked cups formed in palladin KD cells, while no significant difference in Cdc42 recruitment. The recruitment intensity of Apr3 was higher in control cells than palladin KD cells. These results suggested that Palladin participated in the actin dynamics during phagocytic cup formation. We found OCRL is a new Palladin-interacted protein. Palladin interacted with OCRL's 5PPase domain through its third IgC2 domain. Palladin depletion caused a decrease of ~30% OCRL recruitment, retention of PI(4,5)P2, as well as more F-actin at phagosome. These observation suggested that Palladin regulated the recruitment of OCRL at sites of phagosome, and might play an essential role in regulating the hydrolysis of PI(4,5)P2, actin depolymerization and the completion of phagosome closure. CONCLUSIONS: We identify the role of Palladin in phagocytic receptor clustering and Palladin as an early coordinator in actin dynamics during phagosome formation in myeloid cells. Disclosures No relevant conflicts of interest to declare.
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Ellison, Michael A., Daniel R. Ambruso und Gail Thurman. „Peroxiredoxin 6 Enhances Phagocyte NADPH Oxidase (phox) Activity in Response to Agonists Acting Via Cell Surface Receptors and Intracellular Signaling Pathways.“ Blood 120, Nr. 21 (16.11.2012): 2139. http://dx.doi.org/10.1182/blood.v120.21.2139.2139.
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Abstract Abstract 2139 Introduction The phagocyte NADPH oxidase (phox) is a multiprotein, transmembrane-enzyme-complex found in diverse professional phagocytes including neutrophils. Phox in its inactive state consists of the membrane-associated subunit cytochrome b558 (a dimer of gp91phox/Nox2 and p22phox) and cytoplasmic subunits which include p47phox, p67phox, p40phox and Rac1 or Rac2. Phosphorylation of phox proteins promotes tight interaction of the cytoplasmic phox components with cytochrome b558 and the resulting active complex catalyzes transmembrane electron transfer from cytoplasmic NADPH to molecular oxygen forming superoxide anion (O2−). O2− and other reactive oxygen species formed from it are microbicibal and crucial to pathogen killing by neutrophils. Peroxiredoxin 6 (Prdx6) is a bifunctional enzyme with a peroxiredoxin activity that reduces oxidized lipids and H2O2 and a PLA2 activity that cleaves the sn2 position of phospholipids forming the corresponding free fatty acid and lysophospholipid. Previous work in our laboratory has identified Prdx6 as a binding partner of p67phox and as an enhancer of O2− production by active phox; we have shown that this enhancement is due to products of the PLA2 activity of the peroxiredoxin but the precise mechanism by which these molecules act is unclear. Here we present evidence that Prdx6 causes maximal activation of phox when the complex is activated by physiological agonists (the formylated peptide fMLP and the particulate agonist serum opsonized zymosan (SOZ)) but not when it is activated by the non-physiological agonist phorbol 12-myristate 13-acetate (PMA). Because fMLF and SOZ interact with cell surface receptors but PMA enters the cell and activates protein kinase C (PKC) enzymes that directly phosphorylate phox proteins our data provides a clue as to the mode of action of Prdx6 in phox activation. Methods PLB985 cells were used to model neutrophils. This myeloid cell line can be terminally differentiated to a neutrophil like state with phox activity by exposure to DMSO. Prdx6 was suppressed in these cells by stable expression of an shRNA resulting in an approximately 70% reduction of the protein. Following maturation of the cells they were stimulated with fMLP, SOZ or PMA and O2− production was measured by superoxide dismutase (SOD) inhibitable luminescence of Diogenes fluorophore. For fMLP, due to the transient nature of the O2- production, the entire amount of O2− production was measured. SOZ and PMA induced prolonged (>1hr) O2− production and O2− production over 1hr was thus measured. Results In cells with Prdx6 suppressed, SOD inhibitable O2− production in response to fMLP was reduced by 53% ± 3% (SEM), n=34, which was significant (p<0.001). O2− produced in response to SOZ was reduced by 37% ± 9% (SEM), n = 4, which was also significant (p<0.05). In contrast, the response to PMA was not altered (p>0.5, n of at least 4) at a range of PMA concentrations from one causing slight activation of phox (10 ng/ml) to one causing maximal O2- production (1 μg/ml). Conclusions fMLP binds to receptors on neutrophils and triggers intracellular signaling cascades that ultimately lead to phosphorylation and activation of phox. Similarly, opsonins of particulate stimuli bind cell surface complement receptors that trigger intracellular signaling cascades that activate phox. PMA on the other hand enters cells and activates PKC enzymes that directly phosphorylate phox proteins; it thus bypasses the physiological signaling pathways that mediate the fMLP and SOZ response. Since Prdx6 enhances the SOZ and fMLF mediated phox response but not the PMA mediated response we propose that in myeloid cells, products of the PLA2 activity of Prdx6 enhance the SOZ and PMA mediated signaling cascades. This may be via activation of signaling molecules in these pathways which would be consistent with the known ability of the fatty acid arachidonate to activate PKC enzymes, MAP kinases, PLA2 enzymes and a class Ia phosphatidylinositol 3-kinase and to mobilize Ca2+. Disclosures: No relevant conflicts of interest to declare.