The potentiation by TNF-alpha and PMA of Fc receptor-mediated phagocytosis in neutrophils is independent of reactive oxygen metabolites produced by NADPH oxidase and of protein kinase C.
The results presented in this paper demonstrate that the potentiation of phagocytosis of erythrocyte (E) IgG by TNF-alpha or PMA is not due to an oxygen-dependent mechanism. In fact, the potentiation of phagocytosis occurs normally in human neutrophils 1) when the respiratory burst is inhibited by diphenyleneiodonium, 2) in conditions where the reactive oxygen metabolites produced by the activation of NADPH oxidase, that accompanies the phagocytosis, were removed by catalase or superoxide dismutase, 3) of a patient lacking NADPH oxidase activity due to a genetic defect of p67-phox, 4) treated with staurosporine which allowed PMA to potentiate the ingestion of E-IgG at concentrations which inhibited the activation of the respiratory burst. Evidence is also presented that staurosporine not only did not inhibit, but amplified the potentiation of phagocytosis by PMA and TNF-alpha. This last finding suggests that the activation of protein kinase C plays a modulatory rather than a positive role in the mechanism of potentiation of phagocytosis.
Institute of General Pathology, University of Verona, Italy.
V
V
Della Bianca
M
M
Grzeskowiak
E
E
Renzi
F
F
Rossi
D000470:Alkaloids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000097:blood*; D019255:NADPH Oxidases; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D009861:Onium Compounds / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000097:blood*; D011961:Receptors, Fc / Q000187:drug effects / Q000378:metabolism*; D019311:Staurosporine; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000097:blood; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000470:Alkaloids; D007074:Immunoglobulin G; D009861:Onium Compounds; D011961:Receptors, Fc; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; C007517:diphenyleneiodonium; D013482:Superoxide Dismutase; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate