Role of calcium independent phospholipase A2 in the pathogenesis of multiple organ failure

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We have identified biologically active lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) with unsaturated fatty acids (arachidonic acid and linoleic acid) in mesenteric lymph following hemorrhagic shock in rats. It is possible that iPLA2 gamma, the isoform of iPLA2, is involved in the production of these lipid mediators. In addition, we have shown that the iPLA2 gamma specific inhibitor decreases LPC with unsaturated fatty acids in mesenteric lymph and attenuates lung injury after hemorrhagic shock. Also the inhibitor selective for iPLA2 gamma, but not iPLA2 beta and cPLA2, completely inhibited human PMN cytotoxicity (superoxide production, elastase release, and chemotaxis) through receptor signal pathway.The iPLA2 gamma enzyme is activated in the early phase of inflammatory process and regulates PMN cytotoxicity being crucial during inflammation. This enzyme thereby may be closely related to acute inflammation.