Identification of the protease in blood that activates complement factor MASP-3

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07083
• 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: Machida Takeshi 福島県立医科大学, 医学部, 講師 (80583632)
• Co-Investigator(Kenkyū-buntansha): 関根 英治 福島県立医科大学, 医学部, 教授 (40363759)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: MASP-3 / 補体 / 第二経路

Outline of Final Research Achievements

Unlike most complement factors, MASP-3 circulates in an activated form, but the mechanism of activation is unknown. Using recombinant MASP-3, we found that MASP-3 is converted to its activated form in serum and in vivo after intravenous administration in mice. Using the crosslinking co-immunoprecipitation strategy, we identified several molecules that form complexes with MASP-3 at least transiently and examined their ability to activate MASP-3. In addition, we newly found that the physiological significance of complex formation of MASP-3 with recognition molecules of the lectin complement pathway is not its direct contribution to MASP-3 activation, but its role in the long-term retention of MASP-3 in vivo. Our results partially clarified the dynamics of MASP-3 in vivo, which has remained unclear.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

MASP-3は補体第二経路の活性化に必須の因子であり、補体による生体恒常性の維持を担う一方で、補体が無秩序に活性化されると、多くの炎症性疾患を引き起こすことが知られている。これらの疾患における研究で、第二経路の抑制が有効な治療戦略であることが見出されているが、第二経路の他の補体因子であるD因子やB因子は血中濃度が非常に高く、第二経路の最上流に位置し血中濃度が低いMASP-3を標的とした治療戦略は、より効果的で実用的なものとなり得る。本研究では、MASP-3の生体内における動態を一部明らかにしたもので、有効な治療法が確立されていない種々の補体介在性の炎症性疾患の分野において大きな意義を持つ。