Phospholipase A2 activity in human neutrophils. Stimulation by lipopolysaccharide and possible involvement in priming for an enhanced respiratory burst
Forehand, J.R.; Johnston, R.B.; Bomalaski, J.S.
Journal of Immunology 151(9): 4918-4925
1993
ISSN/ISBN: 0022-1767 PMID: 8409449 Document Number: 413355
Exposure to LPS, platelet-activating factor, certain cytokines, and other agents can prime human neutrophils for an increased release of superoxide anion (O-2-) in response to stimuli. Previous work with LPS has suggested that priming may involve alterations in signal transduction pathways related to the release of O-2-. Products derived from the enzymatic activity of phospholipase A-2 (PLA-2) on membrane phospholipids reportedly activate certain of these signaling events. Thus, PLA-2 could play a regulatory role in the release of O-2- by neutrophils. We examined this possibility by studying the effect of LPS on neutrophil PLA-2 activity. Exposure to LPS triggered a fivefold increase in activity of an endogenous PLA-2; control cells incubated under identical conditions without LPS showed no increase. Neutrophil-associated PLA-2 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 PLA-2, blocked LPS priming but not the baseline O-2-, release from unprimed cells. The LPS-provoked increase in PLA-2 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 PLA-2 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 O-2- release at least in part by triggering PLA-2 activity. PLA-2 activation may play a role in regulating production and release of O-2- by the human neutrophil.