Elucidation of the activation mechanism of the complement factor MASP-3 of the alternative complement pathway

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07610
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Sekine Hideharu 福島県立医科大学, 医学部, 教授 (40363759)
• Co-Investigator(Kenkyū-buntansha): 町田 豪 福島県立医科大学, 医学部, 講師 (80583632) ; 林 学 福島県立医科大学, 医学部, 助教 (80745787)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 補体因子 / MASP-3 / 第二経路 / レクチン経路 / 認識分子

Outline of Final Research Achievements

MASP-3 circulates in an active form and forms a complex with recognition molecules of the lectin complex pathway (LP PRMs) in vivo, but its immunological significance is unknown. In this study, four types of mutant recombinant mice MASP-3 (rmMASP-3), which lack the ability to form a complex with LP PRMs, and wild-type rmMASP-3 were administered to mice, and their activation kinetics in vivo were investigated.
As a result, it was found that both of them rapidly changed to the activated forms in the circulation. However, the mutant rmMASP-3 was cleared from the circulation earlier than the wild type rmMASP-3. From these results, it was shown that the complex formation of MASP-3 with LP PRMs is required for the maintenance of MASP-3 in vivo.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究は、第二経路の補体因子であるMASP-3が、なぜレクチン経路の認識分子と複合体を形成するのか、その意義を世界で初めて見出したものであり、補体系のメカニズムの全容解明に大きく貢献する成果である。
補体第二経路は、さまざまな炎症性疾患における増悪因子として知られており、今後MASP-3を標的とする治療戦略を開発する上で、重要な知見をもたらした成果と考えられる。