ATP induces the release of a neutral serine proteinase and enhances the production of superoxide anion in membranes from phorbol ester-activated neutrophils.
Plasma membranes isolated from human neutrophils after brief exposure to phorbol 12-myristate 13-acetate contain a large portion (30-40%) of the total cellular protein kinase C (Melloni, E., Pontremoli, S., Michetti, M., Sacco, O., Sparatore, B., Salamino, F., and Horecker, B. L. (1986) Biochem. Biophys. Res. Commun. 136, 228-234) and also retain almost 90% of their content of neutral serine proteinase (Pontremoli, S., Melloni, E., Michetti, M., Sacco, O., Sparatore, B., Salamino, F., Damiani, G., and Horecker, B. L. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 1685-1689). When ATP is added to the isolated membranes, a substantial amount (approximately 25%) of the intrinsic proteinase is released into the incubation medium. The addition of ATP in the presence of NADPH also caused a significant enhancement of the production of O2 radicals. These effects of ATP were not observed with membranes isolated from untreated neutrophils. The release of the serine proteinase is almost fully dependent on the addition of ATP and is correlated with the phosphorylation of membrane proteins. It is also markedly inhibited by the addition of retinal or trifluoperazine inhibitors of native protein kinase C. The results represent the first direct demonstration of a role for membrane-bound protein kinase C activity in the release of neutral proteinase and the production of O2 radicals, responses related to the cytotoxic effects of activated neutrophils.
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D010450:Endopeptidases / Q000097:blood*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010704:Phorbols / Q000494:pharmacology*; D012172:Retinaldehyde / Q000494:pharmacology; D012697:Serine Endopeptidases; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D010704:Phorbols; D000255:Adenosine Triphosphate; D010450:Endopeptidases; D012697:Serine Endopeptidases; D013755:Tetradecanoylphorbol Acetate; D012172:Retinaldehyde