N-PROTEIN KINASE-C ISOENZYMES MAY BE INVOLVED IN THE REGULATION OF VARIOUS NEUTROPHIL FUNCTIONS

The role of protein kinase C (PKC) isoenzymes in the regulation of cell functions is largely unknown. We studied the effects of 2-(1H-indol-3-yl)-3[1-(3-dimethylaminopropyl)-1H-indol-3-yl] -maleinimide (Go 6850), a selective inhibitor of c- and n-PKC isoenzymes, and 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo[2,3-a]pyrrolo[3,4-c]-carbazole (Go 6976), an inhibitor of c-PKC isoenzymes, on various human neutrophil functions. Go 6850 inhibited 4 beta-phorbol 12-myristate 13-acetate (PMA)-, 1,2-dicaprylyl-glycerol- and chemotactic peptide-induced superoxide anion formation with half-maximal effects at 100 nM, 240 nM and 850 nM, respectively. Go 6850 reverted PMA-mediated inhibition of chemotactic peptide-induced rises in cytosolic Ca2+ concentration with a half-maximal effect at 480 nM. Go 6850 (1 mu M) inhibited PMA-induced lysozyme release by 55%. Go 6976 had no effect on parameters studied. Our data suggest the following: (1) n- Rather than c-PKC isoenzymes are involved in the regulation of various human neutrophil functions. (2) Different n-PKC isoenzymes may mediate activation of NADPH oxidase by various stimuli. (3) Different n-PKC isoenzymes may be involved in the mediation of the effects of PMA on various cell functions. (C) 1994 Academic Press, Inc.