Molecular basis of a new role of ficolin on endogenous homeostasis

• Project/Area Number: 25460596
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Fukushima Medical University
• Principal Investigator: Endo Yuichi 福島県立医科大学, 医学部, 博士研究員 (20117427)
• Research Collaborator: SUZUKI Toshiyuki ; ISHIDA Yumi
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: フィコリン (ficolin) / 自然免疫 / 恒常性維持 / レクチン / レクチン経路 / フィコリン欠損マウス / フィコリン (Ficolin) / 恒常性の維持

Outline of Final Research Achievements

Ficolins are recognition molecules in innate immunity. This study demonstrated that unlike ficolin 2, ficolin 1 was involved in recognition of self-cells in fetal tissues and leukocytes in adult circulation. Ficolin B (mouse ficolin 1) bound to several sialic acid-containing proteins in mouse fetal tissue and adult peripheral leukocytes. Ficolin B also recognized the N-acetyl group of N-terminal amino acid in ubiquitous cytoskeleton proteins in these cells, which are exposed during cell damage. In fetus, ficolin B formed the complex simply with MASP-3, a key enzyme of the lectin pathway, and in adult, ficolin B-MASP complex contained MASP-1, -2, -3, and regulatory proteins sMAP and MAp44. These results suggest that ficolin 1 has a role on endogenous homeostasis through the lectin pathway in both developmental and adult stages.

Research Products

• [Int'l Joint Research] Aarhus University/The Danish Diabetes Academy(デンマーク)
• [Journal Article] Ficolin B in diabetic kidney disease in a mouse model of type 1 diabetes. (2015)
  • Author(s): Holt C B, Østergaard J A, Axelgaard E, Nielsen G K, Endo Y, Thiel S, Hansen T K
  • Journal Title: Mediators Inflamm Volume: 2015 Issue: 1
  • DOI: 10.1155/2015/653260
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Serum syndecan-4 as a possible biomarker in patients with acute pneumonia (2015)
  • Author(s): Nikaido T, Tanino Y, Wang X, Sato S, Misa K, Fukuhara N, Sato Y, Fukuhara A, Uematsu M, Suzuki Y, Kojima T, Tanino M, Endo Y, Tsuchiya K, Kawamura I, Frevert C, Munakata M
  • Journal Title: J Infect Dis Volume: 212 Issue: 9 Pages: 1500-1508
  • DOI: 10.1093/infdis/jiv234
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] New insights into the role of ficolins in the lectin pathway of innate immunity. (2015)
  • Author(s): Endo Y, Matsushita M, Fujita T
  • Journal Title: International Review of Cell and Molecular Biology Volume: 316 Pages: 49-110
  • DOI: 10.1016/bs.ircmb.2015.01.003
  • ISBN: 9780128022818
  • Peer Reviewed / Open Access
• [Journal Article] Purification, measurement of concentration, and functional complement assay of human ficolins. (2014)
  • Author(s): Matsushita M, Kilpatrick D, Shiraki H, Liu Y, Tateishi K, Tsujimura M, Endo Y, Fujita T
  • Journal Title: Methods Mol Biol Volume: 1100 Pages: 141-159
  • DOI: 10.1007/978-1-62703-724-2_12
  • ISBN: 9781627037235, 9781627037242
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Lessons learned from mice deficient in lectin complement pathway molecules. (2014)
  • Author(s): Genster N, Takahashi M, Sekine H, Endo Y, Garred P, Fujita T
  • Journal Title: Mol Immunol Volume: 61 Issue: 2 Pages: 59-68
  • DOI: 10.1016/j.molimm.2014.07.007
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Role of complement in a murine model of peanut-induced anaphylaxis. (2013)
  • Author(s): Kodama T, Sekine H, Takahashi M, Iwaki D, Machida T, Kanno K, Ishida Y, Endo Y, Fujita T
  • Journal Title: Immunobiology Volume: 218 Pages: 844-850
  • Peer Reviewed
• [Journal Article] Mitochondria and the lectin pathway of complement. (2013)
  • Author(s): Brinkmann CR, Jensen L, Dagnæs-Hansen F, Holm IE, Endo Y, Fujita T, Thiel S, Jensenius JC, Degn SE
  • Journal Title: J Biol Chem Volume: 288 Issue: 12 Pages: 8016-8027
  • DOI: 10.1074/jbc.m112.430249
  • Peer Reviewed
• [Journal Article] Comment on "mannan-binding lectin-associated serine protease (MASP)-1 is crucial for lectin pathway activation in human serum, whereas neither MASP-1 nor MASP-3 is required for alternative pathway function" (2013)
  • Author(s): Takahashi M, Sekine H, Endo Y, Fujita T.
  • Journal Title: J Immunol. Volume: 190 Issue: 6 Pages: 2477-2477
  • DOI: 10.4049/jimmunol.1390002
  • Peer Reviewed
• [Journal Article] Structural and functional overview of the lectin complement pathway: its molecular basis and physiological implication. (2013)
  • Author(s): Matsushita M, Endo Y, Fujita T
  • Journal Title: Arch Immunol Ther Exp (Warsz) Volume: 61 Issue: 4 Pages: 273-283
  • DOI: 10.1007/s00005-013-0229-y
  • Peer Reviewed
• [Presentation] MASP-1およびMASP-3の機能-ヒトとマウスのちがいについて.
  • Author(s): 高橋実、遠藤雄一、A. Antonioli, V.M. Holers, W. Schwaeble, 藤田禎三、関根英治
  • Organizer: 第50回補体シンポジウム
  • Place of Presentation: 旭川