The diacylglycerol kinase inhibitor, R59022, enhances the superoxide generation from human neutrophils induced by stimulation of fMet-Leu-Phe, IgG and C3b receptors

Abstract R59022, a specific diacylglycerol kinase inhibitor, at a concentration of 10 −5 M, consistently enhanced superoxide generation from human neutrophils stimulated with fMet-Leu-Phe, IgG, heat-aggregated IgG and opsonized zymosan. The concentration-response curve for fMet-Leu-Phe was displaced to the left and the maximum superoxide release was also consistently increased by R59022 whereas the diacylglycerol iipase inhibitor, RHC80267, 10 −5 M, had no significant effect. These results suggest that the diacylglycerol formed after fMet-Leu-Phe stimulation in human neutrophiis is metabolized largely by the kinase and not the lipase, which implies that diacylglycerol is not the major source of arachidonate during signaltransduction.