2013 Fiscal Year Final Research Report
Role of calcium independent phospholipase A2 in the pathogenesis of multiple organ failure
| Project/Area Number |
23592666
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Emergency medicine
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
AIBOSHI Junichi 東京医科歯科大学, 医学部附属病院, 講師 (50256913)
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| Co-Investigator(Kenkyū-buntansha) |
OTOMO Yasuhiro 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (40176946)
KOBAYASHI Tetsuyuki お茶の水女子大学, 人間文化創成科学研究科, 教授 (50178323)
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| Project Period (FY) |
2011 – 2013
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| Keywords | カルシウム非依存性ホスホリパーゼA２ / 脂質メディエータ / 出血性ショック / 腸管虚血再潅流 / 多臓器不全 / 腸間膜リンパ液 / 好中球 |
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| Research Abstract |
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.
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