Role of H-ficolin. A recognition molecule in innate immunity

• Project/Area Number: 22570144
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Fukushima Medical University
• Principal Investigator: ENDO Yuichi 福島県立医科大学, 医学部, 准教授 (20117427)
• Co-Investigator(Renkei-kenkyūsha): FUJITA Teizo 福島県立医科大学, 名誉教授 (20134223)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 免疫学 / 生体分子 / 蛋白質 / レクチン / 補体 / 成体分子

Research Abstract

To define the role of human H-ficolin in vivo, we generated a model mouse, ficolins A/B double-deficient mouse transiently expressing H-ficolin. In the serum, H-ficolin formed the complexes with serine proteases MASPs and sMAP. H-ficolin recognized a bacterial strain, Streptococcus pneumonia D39, and led to complement activation on this bacterium. The susceptibility of this mouse to bacterial infection is in progress. These results suggest that H-ficolin is involved in first defense against bacterial infection.

Research Products

• [Journal Article] Mouse ficolin B has an ability to form complexes with mannose-binding lectin-associated serine proteases and activate complement through the lectin pathway. (2012)
  • Author(s): Endo Y, Iwaki D, Ishida Y, Takahashi M, Matsushita M, Fujita T.
  • Journal Title: J Biomed Biotech Volume: 2012 Pages: 105891-105891
  • DOI: 10.1155/2012/105891
  • Peer Reviewed
• [Journal Article] Mice Deficient in Ficolin, a Lectin Complement Pathway Recognition Molecule, Are Susceptible to Streptococcus pneumoniae Infection (2012)
  • Author(s): Endo Y, et al.
  • Journal Title: J Immunol Volume: 189 Issue: 12 Pages: 5860-5866
  • DOI: 10.4049/jimmunol.1200836
  • Peer Reviewed
• [Journal Article] L-Ficolin Binds to the Glycoproteins Hemagglutinin and Neuraminidase and Inhibits Influenza A Virus Infection Both in vitro and in vivo (2012)
  • Author(s): Pan Q, et al
  • Journal Title: J Innate Immun Volume: 4(3) Issue: 3 Pages: 312-24
  • DOI: 10.1159/000335670
  • Peer Reviewed
• [Journal Article] The interaction pattern of murine serum ficolin-a with microoganisms (2012)
  • Author(s): Hummelshoj T, Ma YJ, Munthe-Fog L, Bjarnsholt T, Moser C, Skjoedt MO, Romani L, Fujita T, Endo Y and Garred P
  • Journal Title: PLoS One Volume: 7 Issue: 5 Pages: e38196-e38196
  • DOI: 10.1371/journal.pone.0038196
  • Peer Reviewed
• [Journal Article] Microbe-specific c3b deposition in the horseshoe crab complement system in a c2/factor B-dependent or-independent manner (2012)
  • Author(s): Tagawa K, Yoshihara T, Shibata T, Kitazaki K, Endo Y, Fujita T, Koshiba T and Kawabata S.
  • Journal Title: PLoS One Volume: 7 Issue: 5 Pages: e36783-e36783
  • DOI: 10.1371/journal.pone.0036783
  • Peer Reviewed
• [Journal Article] The Lectin Pathway of Complement Activation Is a Critical Component of the Innate Immune Response to Pneumococcal Infection (2012)
  • Author(s): Ali YM, Lynch NJ, Haleem KS, Fujita T, Endo Y, Hansen S, Holmskov U, Takahashi K, Stahl GL, Dudler T, Girija UV, Wallis R, Kadioglu A, Stover CM, Andrew PW, Schwaeble WJ
  • Journal Title: PLoS Pathogens Volume: 8 Issue: 7 Pages: e1002793-e1002793
  • DOI: 10.1371/journal.ppat.1002793
  • Peer Reviewed
• [Journal Article] Guideline for Hereditary Angioedema (HAE) 2010 by the Japanese Association for Complement Research - Secondary Publication (2012)
  • Author(s): Horiuchi T, Ohi H, Ohsawa I, Fujita T,Matsushita M, Okada N, Seya T,Yamamoto T, Endo Y, Hatanaka M,Wakamiya N, Mizuno M, Nakao M, OkadaH, Tsukamoto H, Matsumoto M, Inoue N,Nonaka M, Kinoshita T.
  • Journal Title: Allergology International Volume: 61 Issue: 4 Pages: 559-562
  • DOI: 10.2332/allergolint.12-RAI-0471
  • NAID: 130004873058
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] Mouse ficolin B has an ability to form complexes with mannose-binding lectin-associated serine proteases and activate complement through the lectin pathway (2012)
  • Author(s): Endo Y, Iwaki D, Ishida Y, Takahashi M, Matsushita M, Fujita T.
  • Journal Title: J Biomed Biotech. Volume: 2012
  • Peer Reviewed
• [Journal Article] The role of ficolins in the lectin pathway of innate immunity. (2011)
  • Author(s): Endo Y, Matsushita M, Fujita T.
  • Journal Title: Int J Biochem Cell Biol. Volume: 43 Pages: 705-712
  • Peer Reviewed
• [Journal Article] 補体レクチン経路と凝固系の協調作用-補体系研究の新展開-- (2011)
  • Author(s): 遠藤雄一
  • Journal Title: 日本血栓止血学会誌 Volume: 22 Pages: 164-170
  • NAID: 10031162941
  • Peer Reviewed
• [Journal Article] The role of mannose-binding lectin-associated serine protease-3 in activation of the alternative complement pathway (2011)
  • Author(s): Iwaki D, Kanno K, Takahashi M, Endo Y, Fujita T
  • Journal Title: J Immunol. Volume: 187 Pages: 3751-3758
  • Peer Reviewed
• [Journal Article] Mechanisms of mannose-binding lectin-associated serine proteases-1/3 activation of the alternative pathway of complement. (2011)
  • Author(s): Banda NK, Takahashi M, Takahashi K, Stahl GL, Glogowska M, Wiles TA, Endo Y, Fujita T, Michael Holers V, Arend WP.
  • Journal Title: Mol Immunol Volume: 49 Pages: 281-289
  • Peer Reviewed
• [Journal Article] Interactions of ficolin and mannose-binding lectin with fibrinogen/fibrin augment the lectin complement pathway (2011)
  • Author(s): EndoY, NakazawaN, IwakiD, TakahashiM, MatsushitaM, FujitaT.
  • Journal Title: J Innate Immunity Volume: 2 Pages: 33-42
  • Peer Reviewed
• [Journal Article] Mechanisms of mannose-binding lectin-associated serine proteases-1/3 activation of the alternative pathway of complement (2011)
  • Author(s): Banda NK, Takahashi M, Takahashi K, Stahl GL, Glogowska M, Wiles TA, Endo Y, Fujita T, Michael Holers V, Arend WP
  • Journal Title: Mol Immunol Volume: 49 Pages: 281-289
  • Peer Reviewed
• [Journal Article] The role of mannose-binding lectin-associated serine protease-3 in activation of the alternative complement pathway (2011)
  • Author(s): Iwaki D, Kanno K, Takahashi M, Endo Y, Fujita T
  • Journal Title: J Immunol Volume: 187 Pages: 3751-3758
  • Peer Reviewed
• [Journal Article] The role of ficolins in the lectin pathway of innate immunity (2011)
  • Author(s): Endo Y, Matsushita M, Fujita T
  • Journal Title: Int J Biochem Cell Biol Volume: 43 Pages: 705-712
  • Peer Reviewed
• [Journal Article] 補体レクチン経路と凝固系の協調作用-補体系研究の新展開- (2011)
  • Author(s): 遠藤雄一
  • Journal Title: 日本血栓止血学会誌 Volume: 22 Pages: 164-170
  • NAID: 10031162941
  • Peer Reviewed
• [Journal Article] Essential role of mannose-binding lectin-associated serine protease-1 in activation of the complement factor D. (2010)
  • Author(s): Takahashi M, Ishida Y, Iwaki D, Kanno K, Suzuki T, Endo Y, Homma Y, Fujita T
  • Journal Title: J Exp Med Volume: 207 Pages: 29-37
  • Peer Reviewed
• [Journal Article] Interactions of ficolin and mannose-binding lectin with fibrinogen/fibrin augment the lectin complement pathway. (2010)
  • Author(s): Endo Y, et al.
  • Journal Title: J Innate Immunity Volume: 2 Pages: 33-42
  • Peer Reviewed
• [Presentation] Orthology between human and mouse ficolins, and roles of mouse ficolins A and B in host defense (2012)
  • Author(s): Endo Y, Takahashi M, Matsushita M, Shwaeble WJ, Fujita T.
  • Organizer: 12th Congress of The International Society of Developmental & Comparative Immunology(国際比較免疫学会
  • Place of Presentation: Fukuoka, Japan
• [Presentation] Orthology between human and mouse ficolins, and roles of mouse ficolins A and B in host defense. (2012)
  • Author(s): Endo Y
  • Organizer: 12th Congress of The International Society of Developmental & Comparative Immunology
  • Place of Presentation: Fukuoka
• [Presentation] MASP-3のin vivo 補体第二経路活性化における役割. (2012)
  • Author(s): 兒玉利尚
  • Organizer: 第49回補体シンポジウム
  • Place of Presentation: 大阪
• [Presentation] MASP1/3 欠損マウスにおける形態異常―3MC 症候群との関連. (2012)
  • Author(s): 高橋実
  • Organizer: 第49回補体シンポジウム
  • Place of Presentation: 大阪
• [Presentation] MASP1遺伝子産物の多様性について (2011)
  • Author(s): 高橋実、岩城大輔、遠藤雄一、藤田禎三
  • Organizer: 第48回補体シンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2011-09-03
• [Presentation] 認識分子Ficolin欠損マウスの表現型 (2010)
  • Author(s): 遠藤雄一、松坂友裕、石田由美、岩城大輔、高橋実、松下操、藤田禎三
  • Organizer: 第47回 補体シンポジウム
  • Place of Presentation: 福島
  • Year and Date: 2010-09-10
• [Presentation] TakahashiM, MatsushitaM, Okabe M, FujitaT.Establishment of three lineages of ficolin-deficient mice and their phenotypes (2010)
  • Author(s): Endo Y, NakazawaN, Kanno K, Iwaki D
  • Organizer: 14th International Congress of Immunology (国際免疫学会)
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-24
• [Presentation] Establishment of three lineages of ficolin-deficient mice and their phenotypes (2010)
  • Author(s): Endo Y, et al.
  • Organizer: 第14回 国際免疫学会
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-24
• [Presentation] MASP-3のin vivo 補体第二経路活性化における役割.
  • Author(s): 兒玉利尚、遠藤雄一、高橋実、岩城大輔、藤田禎三、関 根 英 治.
  • Organizer: 第49回補体シンポジウム
  • Place of Presentation: 大阪
• [Presentation] MASP1/3 欠損マウスにおける形態異常-3MC 症候群との関連
  • Author(s): 高橋実、関根英治、遠藤雄一、藤田禎三
  • Organizer: 第49回補体シンポジウム
  • Place of Presentation: 大阪