The effect of inhibition of both diacylglycerol metabolism and phospholipase A2 activity on superoxide generation by human neutrophils

A 'cocktail' consisting of an inhibitor of diacylglycerol kinase (R59022, 10 microM), an inhibitor of diacylglycerol lipase (RHC80267, 10 microM), and an inhibitor of phospholipase A2 (either 100 microM indomethacin, or 100 microM sodium meclofenamate) markedly enhanced superoxide production by human neutrophils stimulated with post-receptor stimuli, fluoride and gamma-hexachlorocyclohexane. On the other hand, the response to the C3b/Fc receptor stimulus, opsonized zymosan, was marginally decreased whilst that to the Fc receptor stimulus, aggregated IgG, was virtually unaffected. Since the inhibitors used are deemed to inhibit the main routes of arachidonate production, these results call into question the role of arachidonate in the transduction of O2- generation by post-receptor stimuli, but support a role for arachidonate in receptor-mediated transduction.