Calphostin C, a specific protein kinase C inhibitor, activates human neutrophils: effect on phospholipase A2 and aggregation.

In this paper we have shown that calphostin C can alone activate phospholipase A2 and induce homotypic aggregation of human neutrophils. Calphostin C stimulated the formation of [3H] platelet-activating factor (PAF) and [14C]arachidonic acid (AA) in prelabeled cells in a time-and concentration-dependent fashion. No significant elevation of intracellular [Ca2+] over the basal level was observed, suggesting a mechanism independent of [Cai2+]. In addition, neutrophil aggregation induced by 500 nM calphostin C was slightly inhibited by PAF antagonist BN 50739 but not by WEB 2086, a less potent PAF antagonist. Also, mepacrine, a phospholipase A2 inhibitor and nordihydroguaretic acid (NDGA), a lipoxygenase inhibitor, were unable to inhibit calphostin C-induced neutrophil aggregation. This suggests a dissociation between PLA2 activation and aggregation by calphostin C in human neutrophils.