Roles of calcium-independent phospholipase A2 in sepsis-associated disseminated intravascular coagulation

Research Project

Project/Area Number	17K11567
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Emergency medicine
Research Institution	Tokyo Medical and Dental University
Principal Investigator	Aiboshi Junichi 東京医科歯科大学, 医学部附属病院, 講師 (50256913)
Co-Investigator(Kenkyū-buntansha)	小林哲幸お茶の水女子大学, 基幹研究院, 教授 (50178323)
Project Period (FY)	2017-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000) Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000) Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000) Fiscal Year 2017: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywords	カルシウム非依存性ホスホリパーゼA2 / 血小板 / 敗血症 / 播種性血管内凝固症候群 / カルシウム非依存性PLA2 / DIC
Outline of Final Research Achievements	There are cytosolic PLA2 (cPLA2) and calcium-independent PLA2 (iPLA2β and iPLA2γ) in the cytoplasm of human platelets. In general, cPLA2 activated with collagen, adenosine diphosphate, etc. produces arachidonic acid and eicosanoids, which play a crucial role in the process of platelet aggregation; roles of iPLA2 on platelet activation are ill-defined. Our study has demonstrated that iPLA2, especially iPLA2β, is strongly related to human platelet function (aggregation, degranulation, eicosanoid production, activation of intrinsic clotting system) in response to thrombin.
Academic Significance and Societal Importance of the Research Achievements	重症敗血症に伴う播種生血管内凝固症候群（disseminated intravascular coagulation; DIC）は、過剰な凝固系の活性化によって産生されたトロンビンが全身性の血栓形成を促進し、多臓器不全に至る疾患である。非常に致死的な病態であるにもかかわらず、十分な治療効果を示す治療薬は限られている。本研究の結果から、iPLA2、特にiPLA2βに対する阻害は、敗血症性DICに対する治療戦略の一つになることが示唆された。