Does protein kinase C control receptor-mediated phagocytosis in human neutrophils?
It was previously demonstrated that C3bi- but not IgG-mediated phagocytosis in human neutrophils is a Ca2+-independent process [(1985) Nature 315, 509-511]. The objective of this study was to elucidate the nature of an additional messenger signal(s) that may be involved in receptor-mediated phagocytosis in these cells. The C3bi- and IgG-mediated phagocytic ability of neutrophils was inhibited by forskolin, a potent activator of adenylate cyclase. It was found that forskolin induced a 3-fold increase in cAMP levels and simultaneously reduced the uptake of both C3bi- and IgG-opsonized particles by 65%. This inhibition was reversed by exposure to either phorbol myristate acetate (PMA) or diacylglycerol (OAG), which are both activators of protein kinase C, but not by the inactive analog 4 alpha-PMA. PMA could also restore the phagocytic ability of neutrophils with an experimentally impaired calcium response. These results suggest that activation of protein kinase C might be an important transducing signal controlling receptor-mediated phagocytosis in human neutrophils.
Andersson
T
T
Department of Medical Microbiology, University of Linköping, Sweden.
Fällman
M
M
Lew
D P
DP
Stendahl
O
O
D000242:Cyclic AMP / Q000097:blood; D004075:Diglycerides / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D010587:Phagocytosis; D011493:Protein Kinase C / Q000097:blood* / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D011971:Receptors, Immunologic; C038237:1-oleoyl-2-acetylglycerol; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate