Hyperglycemia-induced protein kinase C activation inhibits phagocytosis of C3b- and immunoglobulin g-opsonized yeast particles in normal human neutrophils.
The aim of this study was to investigate the effects of elevated glucose concentrations on complement receptor- and Fcgamma receptor-mediated phagocytosis in normal human neutrophils. D-Glucose at 15 or 25 mM dose-dependently inhibited both complement receptor- and Fcgamma receptor-mediated phagocytosis, as compared to that at a normal physiological glucose concentration. The protein kinase C (PKC) inhibitors GF109203X and Go6976 both dose-dependently and completely reversed the inhibitory effect of 25 mM D-glucose on phagocytosis. Complement receptor-mediated phagocytosis was dose-dependently inhibited by the cell permeable diacylglycerol analogue 1,2-dioctanoyl-sn-glycerol (DAG), an effect that was abolished by PKC inhibitors. Furthermore, suboptimal inhibitory concentrations of DAG and glucose showed an additive inhibitory effect on complement receptor-mediated phagocytosis. The authors conclude that elevated glucose concentrations can inhibit complement receptor and Fcgamma receptor-mediated phagocytosis in normal human neutrophils by activating PKCalpha and/or PKCbeta, an effect possibly mediated by DAG.
Saiepour
Daniel
D
Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umeå University, Umeå, Sweden.
Sehlin
Janove
J
Oldenborg
Per-Arne
PA
D002227:Carbazoles / Q000494:pharmacology; D003179:Complement C3b / Q000502:physiology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000382:microbiology; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000097:blood*; D012441:Saccharomyces cerevisiae
D002227:Carbazoles; D004791:Enzyme Inhibitors; D007074:Immunoglobulin G; D007211:Indoles; D008301:Maleimides; C081021:Go 6976; D003179:Complement C3b; D011493:Protein Kinase C; C070515:bisindolylmaleimide I