Novel mechanism of complement activation by membrane-type collectin CL-P1

2021 Fiscal Year Final Research Report

• Project/Area Number: 17K08615
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Rakuno Gakuen University (2018-2021); Asahikawa Medical College (2017)
• Principal Investigator: Ohtani Katsuki 酪農学園大学, 農食環境学群, 教授 (90396367)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Keywords: 補体 / コレクチン / スカベンジャー受容体 / 血管障害

Outline of Final Research Achievements

I attempted to prove the mechanism of membrane-type collectin CL-P1-mediated complement activation in vivo using wild-type mice, and demonstrated by fluorescent immunostaining that complement factor C1q binds to pentraxin in a concentration-dependent manner, activating the complement pathway and forming a membrane-damaging complex. Furthermore, by overexpressing CL-P1 in various human vascular endothelial cells and adding human CFH-deficient serum, I attempted to reproduce cellular injury in vitro and confirmed complement activation, although the reactivity differed from cell to cell. Although CL-P1 expression was not upregulated, I found that inflammatory cytokines induced the deposition of complement factor C3 on the cell surface, leading to MAC formation.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

補体活性化経路において膜結合型コレクチンCL-P1が活性化に寄与する報告はなく、新たな補体活性化メカニズムの提供に寄与する成果である。今後他の補体関連因子との関連性について研究が進むことにより新たな役割の解明が期待される。
臨床的には原因不明の血管障害に新たなメカニズムを提案し、発症のメカニズムが解明されていない関連疾患の解明や治療戦略において重要な知見を提供する研究である。