Novel mechanism of complement activation by membrane-type collectin CL-P1
| Project/Area Number |
17K08615
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Rakuno Gakuen University (2018-2021)
Asahikawa Medical College (2017) |
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Principal Investigator |
Ohtani Katsuki 酪農学園大学, 農食環境学群, 教授 (90396367)
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| Project Period (FY) |
2017-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 補体 / コレクチン / スカベンジャー受容体 / 血管障害 / 免疫学 / 炎症 |
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| 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.
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| 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。
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Report
(6 results)
Research Products
(34 results)
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[Journal Article] Disseminated Gonococcal Infection in a Japanese Man with Complement 7 deficiency with compound heterozygous variants.2021
Author(s)
Kageyama, M., Hagiya, H., Ueda, Y., Ohtani, K., Fukumori, Y., Inoue, N., Wakamiya, N., Yoneda, N., Kimura, K., Nagasawa, M., Nakagami, F., Nishi, I., Sugimoto, K., Rakugi H.
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Journal Title
Medicine
Volume: 100
Issue: 13
Pages: e25265-e25265
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] 移植後早期の補体Ba上昇は移植関連血栓性微小血管症の発症予測マーカーになり得る2021
Author(s)
岡山 裕介, 岡村 浩史, 中前 博久, 進藤 岳郎, 大谷 克城, 日高 義彦, 大塚 泰史, 幕内 陽介, 久野 雅智, 高桑 輝人, 原田 尚憲, 西本 光孝, 中嶋 康博, 康 秀男, 廣瀬 朝生, 中前 美佳, 日野 雅之, 若宮 伸隆, 井上 徳光
Organizer
第57回 日本補体学会学術集会
Related Report
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[Presentation] 同種造血細胞移植後早期の補体Ba上昇は移植関連血栓性微小血管症の発症予測マーカーになり得る2020
Author(s)
岡村 浩史, 中前 博久, 進藤 岳郎, 大谷 克城, 日高 義彦, 大塚 泰史, 南野 智, 中嶋 康博, 康 秀男, 廣瀬 朝生, 中前 美佳, 日野 雅之, 若宮 伸隆, 井上 徳光
Organizer
日本移植学会
Related Report
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[Presentation] Comprehensive analysis of complement proteins and genes in thrombotic microangiopathy in Japan2018
Author(s)
Hidaka, Y., Inoue, N., Ohtani, K., Ohtsuka, Y., Sawai, T., Miyata, T., Ohsawa, I., Okada, H., Kinoshita, T., Sekine, H., Tsukamoto, H., Nakao, M., Mizuno, M., Murakami, Y., Horiuchi, T., Wakamiya, N.
Organizer
International Complement Workshop
Related Report
Int'l Joint Research
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