Physiological role of ficolin, a pattern-recognition molecule

• Project/Area Number: 18590476
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Fukushima Medical University
• Principal Investigator: ENDO Yuichi Fukushima Medical University, 医学部, 准教授 (20117427)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥630,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
• Keywords: 自然免疫 / 生体防御 / フィコリン / レクチン経路 / 補体 / フィ懲りん(Ficolin) / レクチン / フィコリン(Ficolin)

Research Abstract

フィコリン(Ficolin)の生理的役割を明らかにするために、フィコリン欠損マウスを作製し、細菌感染に対する抵抗性などの表現型を解析した。その結果、フィコリンAは、セリンプロテアーゼMASPと複合体を形成し、補体レクチン経路を活性化して、細菌など非自己の補体によるオプソニン化とその排除に寄与していることが明らかになった。とくに、肺炎の主な原因細菌である肺炎球菌の感染防御に関してはフィコリンが中心的役割を持つことが判明した。

Research Products

• [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 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, Nakazawa N, Iwaki D, Takahashi M, Matsushita M, Fujita T.
  • Journal Title: J Innate Immunity 2 Pages: 33-42
  • Peer Reviewed
• [Journal Article] Unique phenotypes of Cls-deficiency/abnormality caused by two compound heterozygosities in a Japanese family (2009)
  • Author(s): Abe K, Endo Y, Nakazawa N, Kazuko K, Okubo M, Hoshino T, Fujita T.
  • Journal Title: J Immunol 182 Pages: 1681-1688
  • Peer Reviewed
• [Journal Article] Unique phenotypes of Cls-deficiency/abnormality caused by two compound heterozygosities in a Japanese family. (2009)
  • Author(s): Abe K, et al.
  • Journal Title: J Immunol 182 Pages: 1681-1688
  • Peer Reviewed
• [Journal Article] パターン認識分子としてのフィコリン (2009)
  • Author(s): 遠藤雄一, ほか
  • Journal Title: 日本細菌学雑誌 63 Pages: 399-405
  • NAID: 10025863561
  • Peer Reviewed
• [Journal Article] Factor C Acts as a Lipopolysaccharide-Responsive C3 Convertase in Horseshoe Crab Complement Activation (2008)
  • Author(s): Ariki S, Takahara S, Shibata T, Fukuoka T, Ozaki A, Endo Y, Fujita T, Koshiba T, Kawabata S.
  • Journal Title: J Immunol 181 Pages: 7994-8001
  • Peer Reviewed
• [Journal Article] Mannose-binding lectin (MBL)-associated serine protease (MASP)-1 contributes to activation of the lectin complement pathway (2008)
  • Author(s): Takahashi M, Iwaki D, Kanno K, Ishida Y, Xiong J, Matsushita M, Endo Y, Miura S, Ishii N, Sugamura K, Fujita T.
  • Journal Title: J Immunol 180 Pages: 6132-6138
  • Peer Reviewed
• [Journal Article] Mannose-binding lectin (MBL)-associated serine protease (MASP)-1 contributes to activation of the lectin complement pathway. (2008)
  • Author(s): Takahashi M, et al.
  • Journal Title: J Immunol 180 Pages: 6132-6138
  • Peer Reviewed
• [Journal Article] Factor C Acts as a Lipopolysaccharide-Responsive C3 Convertase in Horseshoe Crab Complement Activation. (2008)
  • Author(s): Ariki S, et al.
  • Journal Title: J Immunol 181 Pages: 7994-8001
  • Peer Reviewed
• [Journal Article] マンノース結合レクチン(MBL)とフィコリン(ficolin)の構造と機能. (2008)
  • Author(s): 遠藤雄一, ほか
  • Journal Title: 臨床検査 52 Pages: 841-850
  • Peer Reviewed
• [Journal Article] Mannose-binding lectin (MBL)-associated serine-protease (HASP)-1 contributes activation of the lectin complement pathway. (2008)
  • Author(s): Takahashi M, et. al.
  • Journal Title: J Immunol (in press)
  • Peer Reviewed
• [Journal Article] Role of ficolin in innate immunity and its molecular basis (2007)
  • Author(s): Endo Y, Matsushita M, Fujita T.
  • Journal Title: Immunobiology 212 Pages: 371-379
  • Peer Reviewed
• [Journal Article] Stat3 is involved in control of MASP2 gene expression (2007)
  • Author(s): Unterberger C, Hanson S, Klingenhoff A, Oesterle D, Frankenberger M, Endo Y, Matsushita M, Fujita T, Schwaeble W, Weiss EH, Ziegler-Heitbrock L, Stover C.
  • Journal Title: Biochem Biophys Res Commun 364 Pages: 1022-1025
  • Peer Reviewed
• [Journal Article] Structural insights into the innate immune recognition specificities of L- and H-ficolins (2007)
  • Author(s): Garlatti V, Belloy N, Martin L, Lacroix M, Matsushita M, Endo Y, Fujita T, Fontecilla-Camps JC, Arlaud GJ, Thielens NM, Gaboriaud C.
  • Journal Title: EMBO J 26 Pages: 623-633
  • Peer Reviewed
• [Journal Article] Role of ficolin in innate immunity and its molecular basis. (2007)
  • Author(s): Endo Y, et. al.
  • Journal Title: Immunobiology 212 Pages: 371-379
  • Peer Reviewed
• [Journal Article] Stat3 is involved in control of MASP2 gene expression. (2007)
  • Author(s): Unterberger C, et. al.
  • Journal Title: Biochem Biophys Res Commun 364 Pages: 1022-1025
  • Peer Reviewed
• [Journal Article] Structural insights into the innate immune recognition specificities of L- and H- ficolins. (2007)
  • Author(s): Garlatti V. et al.
  • Journal Title: EMBO J. 26 Pages: 623-633
• [Journal Article] Structure and Function of ficolins (2006)
  • Author(s): Endo Y, Liu Y, Fujita T.
  • Journal Title: Adv Exp Biol Med 586 Pages: 265-279
  • Peer Reviewed
• [Journal Article] Lectin complement system and pattan recognition (2006)
  • Author(s): Endo Y, Takahashi M, Fujita T.
  • Journal Title: Immunobiology 211 Pages: 283-293
  • Peer Reviewed
• [Journal Article] Small mannose-binding lectin-associated protein plays a regulatory role in the lectin complement pathway (2006)
  • Author(s): Iwaki D, Kanno K, Takahashi M, Endo Y, Lynch NJ, Schwaeble WJ, Matsushita M, Okabe M, Fujita T.
  • Journal Title: J Immunol 177 Pages: 8626-32
  • Peer Reviewed
• [Journal Article] Molecular basis of clonal expansion of hematopoiesis in two patients with paroxysmal nocturnal hemoglobinuria (PNH) (2006)
  • Author(s): Inoue N, Izui-Sarumaru T, Murakami Y, Endo Y, Nishimura J, Kurokawa K, Kuwayama M, Shime H, Machii T, Kanakura Y, Meyers G, Wittwer C, Chen Z, Babcock W, Frei-Lahr D, Parker C, Kinoshita T.
  • Journal Title: Blood 108 Pages: 4232-6
  • Peer Reviewed
• [Journal Article] Single nucleotide polymorphisms of ficolin 2 gene in Behcet's disease (2006)
  • Author(s): Chen X, Katoh Y, Nakamura K, Oyama N, Kaneko F, Endo Y, Fujita T, Nishida T, Mizuki N.
  • Journal Title: J.Dermatol.Sci 43 Pages: 201-205
  • NAID: 10020548762
  • Peer Reviewed
• [Journal Article] Cloning and characterization of mannose-binding lectin from lamprey (Agnathans) (2006)
  • Author(s): Takahashi M, Iwaki D, Matsushita A, Nakata M, Matsushita M, Endo Y, Fujita T.
  • Journal Title: J Immunol 176 Pages: 4861-4868
  • Peer Reviewed
• [Journal Article] Structure and function of ficolins. (2006)
  • Author(s): Endo Y.et al.
  • Journal Title: Adv. Exp. Biol. Med. 586 Pages: 265-279
• [Journal Article] Lectin complement system and pattan recognition. (2006)
  • Author(s): Endo Y.et al.
  • Journal Title: Immunobiol. 211 Pages: 283-293
• [Journal Article] Cloning and characterization of mannose-binding lectin from lamprey (Agnathans). (2006)
  • Author(s): Takahashi M. et al.
  • Journal Title: J Immunol 176 Pages: 4861-4868
• [Journal Article] Small mannose-binding lectin-associated protein plays a regulatory role in the lectin complement pathway. (2006)
  • Author(s): Iwaki D. et al.
  • Journal Title: J. Immunol. 177 Pages: 8626-8632
• [Journal Article] Single nucleotide polymorphisms of ficolin 2 gene in Behcet's disease. (2006)
  • Author(s): Chen X.et al.
  • Journal Title: J. Dermatol. Sci. 43 Pages: 201-205
• [Journal Article] Molecular cloning and characterization of novel splicing variants of human decay-accelerating factor. (2006)
  • Author(s): Osuka F. et al.
  • Journal Title: Genomics 88 Pages: 316-322
• [Journal Article] Identification of the decay-accelerating factor CD55 as a peanut agglutinin-binding protein and its alteration in non-small lung cancers. (2006)
  • Author(s): Higuchi M. et al.
  • Journal Title: Clin. Cancer Res. 12 Pages: 6367-6372
• [Journal Article] Molecular basis of clonal expansion of hematopoiesis in two patients with paroxysmal nocturnal hemoglobinuria(PNH). (2006)
  • Author(s): Inoue N. et al.
  • Journal Title: Blood 108 Pages: 4232-4236
• [Presentation] 補体レクチン経路の分子基盤と系統発生 (2009)
  • Author(s): 遠藤雄一, 岩城大輔, 高橋実, 松下操, 藤田禎三
  • Organizer: 第46回補体シンポジウム
  • Place of Presentation: 福岡
  • Year and Date: 2009-08-22
• [Presentation] 補体Cls欠損症の遺伝子解析 : 新たなミツセンス変異を含むCls異常の一家系 (2008)
  • Author(s): 中澤なおみ, ほか
  • Organizer: 第45回補体シンポジウム
  • Place of Presentation: 札幌
  • Year and Date: 2008-07-10
• [Presentation] 認識分子フィコリンの構造と働き (2007)
  • Author(s): 遠藤雄一, 岩城大輔, 高橋実, 松下操, 藤田禎三
  • Organizer: 第44回補体シンポジウム
  • Place of Presentation: 平塚
  • Year and Date: 2007-08-24
• [Presentation] 生体防御レクチンシンポジウム:認識分子Ficolinの構造と働き (2007)
  • Author(s): 遠藤雄一
  • Organizer: 第44回補体シンポジウム
  • Place of Presentation: 神奈川県平塚市
  • Year and Date: 2007-08-24
• [Presentation] Ficolin A functions to eliminate pathogens through the lectin complement pathway (2006)
  • Author(s): Endo Y, Nakazawa N, Kanno K, Liu Y, Iwaki D, Takahashi M, Nakata M, Matsushita M, Okabe M, Fujita T.
  • Organizer: XXIst International Complement Workshop
  • Place of Presentation: Beijing : Molecular Immunology
  • Year and Date: 2006-10-23
• [Book] Animal Lectins : A Functional View(Ficolins : The structural basis for recognition plasticity. Vasta G R and Ahmed H eds) (2008)
  • Author(s): Matsushita M, Endo Y, Fujita T.
  • Publisher: CRC Press
• [Book] Animal Lectins : A Functional View (2008)
  • Author(s): Matsushita M, et al.
  • Publisher: Ficolins : The structural basis for recognition plasticity.