Phospholipase A2 activity in human neutrophils. Stimulation by lipopolysaccharide and possible involvement in priming for an enhanced respiratory burst.

Exposure to LPS, platelet-activating factor, certain cytokines, and other agents can prime human neutrophils for an increased release of superoxide anion (O2-) in response to stimuli. Previous work with LPS has suggested that priming may involve alterations in signal transduction pathways related to the release of O2-. Products derived from the enzymatic activity of phospholipase A2 (PLA2) on membrane phospholipids reportedly activate certain of these signaling events. Thus, PLA2 could play a regulatory role in the release of O2- by neutrophils. We examined this possibility by studying the effect of LPS on neutrophil PLA2 activity. Exposure to LPS triggered a fivefold increase in activity of an endogenous PLA2; control cells incubated under identical conditions without LPS showed no increase. Neutrophil-associated PLA2 activity increased 5 to 10 min after the addition of LPS to the cells and preceded the emergence of the primed state. Quinacrine and p-bromophenacylbromide, inhibitors of PLA2, blocked LPS priming but not the baseline O2- release from unprimed cells. The LPS-provoked increase in PLA2 activity resulted in release of oleic acid (38 +/- 4% above baseline) but not arachidonic, linoleic, or palmitic acid. In contrast, ionomycin resulted in significant release of all four fatty acids. The addition of exogenous PLA2 to neutrophils primed them. Priming was rapid and was 80 +/- 5% complete within 3 min. Thus, LPS and perhaps other agents may mediate their effects on O2- release at least in part by triggering PLA2 activity. PLA2 activation may play a role in regulating production and release of O2- by the human neutrophil.