Elucidation of the relationship between the platelet receptor CLEC-2 and the pathophysiology of sepsis and its application as a new therapeutic target

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16185
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: University of Yamanashi
• Principal Investigator: SASAKI Tomoyuki 山梨大学, 大学院総合研究部, 准教授 (40739124)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: CLEC-2 / 血小板 / 敗血症 / 好中球 / NETs

Outline of Final Research Achievements

In the present study, we used a mouse model of sepsis and a model of neutrophil NETs formation to elucidate the role of the platelet-activated receptor CLEC-2 in the pathogenesis of sepsis. As a result, the survival rate due to platelet CLEC-2 expression in the sepsis model differed in the induction method. Induction by appendectomy significantly prolonged survival with CLEC-2 deficiency, but no difference was observed with LPS administration. In neutrophil NETs formation, co-culture with LPS and platelets induced NETs formation and was further inhibited by CLEC-2 blockers. This indicates that platelet CLEC-2 contributes to the formation of neutrophil NETs, which are involved in innate immunity.

Free Research Field

血栓止血学

Academic Significance and Societal Importance of the Research Achievements

血小板CLEC-2の病態生理学的役割は，血小板血栓の形成のみならず，血栓の安定化，癌の転移に寄与することが報告されていたが，敗血症との関連は不明であった．本研究において，血小板CLEC-2が敗血症と好中球のNETs形成に寄与することが示唆された．そのメカニズムなどのさらなる解析を進める必要はあるが，血小板CLEC-2が抗血小板効果と抗NETs形成効果の両者によって敗血症性DICへの新たな治療標的となる可能性がある．