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Elucidation of activation mechanism of the lectin complement pathway

Research Project

Project/Area Number 08670372
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionFukushima Medical University

Principal Investigator

MATSUSHITA Misao  Fukushima Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (00165812)

Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywordscomplement / lectin pathway / MBL / MASP / sMAP / マンノース結合蛋白 / P22
Research Abstract

Mannose-binding lectin (MBL, also called MBP) is associated with two types of serine protease, MASP-1 and MASP-2, which are structually homologous. Upon binding to carbohydrates such as mannose on pathogens, the MBL-MASP complex activates the lectin complement pathway. The aim of this research was to elucidate the activation mechamism of the lectin pathway. We obtained the following results.
1) A 22kDa protein (sMAP) is present in an MBL-MASP preparation and is associated with MASP-1. cDNA analysis of sMAP revealed that sMAP is derived from the MASP-2 gene by alternative polyadenylation.
2) We developed an ELISA for MASP-1 levels in human serum and found that MBL and MASP-1 levels in serum are not correlated in the individual, and that MASP-1 exists as MBL-bound and MBL-unbound forms, the latter of which is associated with sMAP in part.
3) MASP-1 and MASP-2 exhibit proteolytic activities towards C3 and C4, respectively.
4) MBL exists as a homopolymer with various sizes. Analysis of one of MBL homopolymers revealed that it copurified with MASP-1 and sMAP but not with MASP-2.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (44 results)

All Other

All Publications (44 results)

  • [Publications] Endo, Y.: "Exon structure of the gene encoding the human mannose-binding protein-associated serine protease(MASP) light chain : comparison with complement" Int. Immunol.8. 1355-1358 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Matsushita, M.: "The lectin pathway." Res. Immunol.147. 115-118 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Matsushita, M.: "The lectin pathway of the complement system." Microbiol. Immunol.40. 887-893 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 松下 操: "補体研究の新展開-レクチン経路の意義-" 感染、炎症、免疫. 26. 136-143 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Terai, I.: "Human serum mannose-binding lectin(MBL)-associated serine protease-1(MASP-1) : Determination of levels in body fluids and identification of two forms in serum." Clin. Exp. Immunol.110. 317-323 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sato, R.: "Substances reactive with mannose‐binding protein(MBP) in sera of patients with rheumatoid arthritis." Fukushima, J. Med. Sci.43. 99-111 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 松下 操: "補体の第三経路" リウマチ科. 18. 293-299 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 松下 操: "補体系の進歩-レクチン経路の発見とその意義" Biomedical Perspectives. 6. 446-453 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Endo, M.: "Glomerular deposition of mannose-binding lectin(MBL) indicates a novel mechanism of complement activation in IgA nephropathy." Nephrol. Dial. Transplant.13. 1984-1990 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Matsushita, M.: "Association of mannose-binding lectin gene haplotype LXPA and LYPB with interferon-resistant hepatitis C virus infection in Japanese patients." J. Hepatol.29. 695-700 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Endo, Y.: "Two lineages of mannose-binding lectin-associated serine protease(MASP) in vertebrates." J. Immunol.161. 4924-4930 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Matsushita, M.: "MASP1(MBL-assocated serine protease 1)" Immunobiol.199. 340-347 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Matsushita, M.: "Complement-related serine proteases in tunicates and vertebrates." Curr. Opin. Immunol.10. 29-35 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 松下 操: "補体活性化のレクチン経路とその生体における意義" 臨床免疫. 30. 905-911 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nonaka, M.: "Opsonic complement component C3 in the solitary ascidian, Halocynthia roretzi." J. Immunol.162. 387-391 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 松下 操: "補体活性化機構" 日本臨床. 57. 291-297 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takahashi, M.: "A truncated form of mannose-binding lectin-associated serine protease-2(MASP-2) expressed by alternative polyadenylation is a component of the lectin complement pathway." Int. Immunol.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 松下 操: "補体検査 -MBL欠損症について-" 臨床検査. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Matsushita. M. (分担執筆): "Collectins and Innate Immunity" Ezekowitz, R. A. B., Sastry, K. and Reid, K. B. M. R. G. Landers Co. Austin, U. S. A. 編, 189 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 松下 操(分担執筆): "異物識別と生体反応" 日本生体防御学会 岡田秀親編 菜根出版, (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Endo, Y.: "Exon structure of the gene encoding the human mannose-binding protein-associated serine protease (MASP) light chain : comparison with complement C1r and C1s genes." Int.Immunol.8. 1355-1358 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Matsuhita, M.: "The lectin pathway." Res.Immunol.147. 115-118 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Matsushita, M.: "The lectin pathway of the complement system." Microbiol. Immunol.40. 887-893 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Terai, I.: "Human serum mannose-binding lectin (MBL)-associated serine protease-1 (MASP-1) : Determination of levels in body fluids and identification of two forms in serum." Clin.Exp.Immunol.110. 317-323 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sato, R.: "Substances reactive with mannose-binding protein (MBP) in sera of patients with rheumatoid arthritis." Fukushima, J.Med.Sci.43. 99-111 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Endo, M.: "Glomerular deposition of mannose-binding lectin (MBL) indicates a novel mechanism of complement activation in IgA nephropathy." Nephrol. Dial. Transplant. 13. 1984-1990 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Matsushita, M.: "Association of mannose-binding lectin gene haplotype LXPA and LYPB with interferon-resistant hepatitis C virus infection in Japanese patients." J.Hepatol.29. 695-700 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Endo, Y.: "Two lineages of mannose-binding lectin-associated serine protease (MASP) in vertebrates." J.Immunol.161. 4924-4930 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Matsushita, M.: "MASP1 (MBL-assocated serine protease 1)" Immunobiol.199. 340-347 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Matsushita, M.: "Complement-related serine proteases in tunicates and vertebrates." Curr.Opin.Immunol.10. 29-35 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nonaka, M.: "Opsonic complement component C3 in the solitary ascidian, Halocynthia roretzi." J.Immunol.162. 387-391 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takahashi, M: "A truncated form of mannose-binding lectin-associated serine protease-2 (MASP-2) expressed by alternative polyadenylation is a component of the lectin complement pathway." Int.Immunol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Terai Itaru: "Human serum mannose-binding lectin(MBL)-associated serine protease 1(MASP-1):Determination of levels in body fluids and identification of two forms in serum." Clinical and Experimental Immunology. 110. 317-323 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Matsushita Misao: "Complement-related serine proteases in tunicates and vertebrates." Carrent Opinion in Immunology. 10. 29-35 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Matsushita Misao: "MASP1" Immunobiology. (印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 松下 操: "補体活性化のレクチン経路とその生体における意義" 臨床免疫. (印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 松下 操: "補体系の進歩-レクチン経路の発見とその意義" Biomedical Perspectives. 6. 114-121 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sato Rika: "Substances reactive with mannose-binding protein(MBP)in sera of patients with Rheumatoid Arthritis" Fukushima J.Med.Sci.(印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Misao Matsushita: "A novel human serum lectin with collagen-and fibrinogen-like domain that functions as an opsonin." Journal of Biological Chemistry. 271. 2448-2454 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Misao Matsushita: "The loctin pathway" Research in Immunology. 147. 115-118 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Misao Matsushita: "The lectin pathway of the complement system" Microbiology and Immunology. 40. 887-893 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 松下 操: "補体研究の新展開 -レクチン経路の意義-" 感染・炎症・免疫. 26. 18-25 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 松下 操: "補体の第三経路" リウマチ科. (印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yuichi Endo: "Exon structure of the gene encoding the human mannuse-binding protein-associated serine protease (MASP) light chain : comparison with complement clranceci genes" International Immunology. 8. 1355-1358 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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