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

我们在失血性休克大鼠肠系膜淋巴中鉴定了具有生物活性的溶血磷脂酰胆碱(LPC)和溶血磷脂酰乙醇胺(LPE)及其不饱和脂肪酸(花生四烯酸和亚油酸)。IPLA2的异构体iPLA2-γ可能参与了这些脂质介质的产生。此外，我们还发现iPLA2γ特异性抑制剂可降低肠系膜淋巴中含有不饱和脂肪酸的LPC，从而减轻失血性休克后的肺损伤。此外，iPLA2γ的选择性抑制剂，而不是iPLA2β和cPLA2，通过受体信号通路完全抑制人PMN的细胞毒性(超氧化物产生、弹性酶释放和趋化)。iPLA2伽马酶在炎症过程的早期被激活，并调节在炎症过程中至关重要的PMN细胞毒性。因此，这种酶可能与急性炎症密切相关。

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.