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.
Svetlov
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Department of Gynecology, Universitatsklinikum Steglitz, Free University Berlin, Germany.
Nigam
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S
D016718:Arachidonic Acid / Q000096:biosynthesis; D002118:Calcium / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D016257:Fura-2; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009281:Naphthalenes; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000096:biosynthesis; D011083:Polycyclic Compounds / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*
D009281:Naphthalenes; D010972:Platelet Activating Factor; D011083:Polycyclic Compounds; D016718:Arachidonic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; C058819:calphostin C; D002118:Calcium; D016257:Fura-2