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A novel lectin-dependent activation pathway of complement

Research Project

Project/Area Number 07044285
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionFukushima Medical College

Principal Investigator

FUJITA Teizo  Department of Biochemistry, Fukushima Medical College, 医学部, 教授 (20134223)

Co-Investigator(Kenkyū-buntansha) リード ケネス  オックスフォード大学, MRC, 教授
エゼユビッツ アラン  ハーバード大学, 医学部, 教授
MIZUOCHI Tsuguo  Department of Applied Chemistry, Tokai University, 工学部, 教授 (90133149)
KOBYASHI Kunihiko  Department of Pediatrics, Hokkaido University School of Medicine, 医学部, 教授 (60091451)
MATSUSHITA Misao  Department of Biochemistry, Fukushima Medical College, 医学部, 講師 (00165812)
EZEKOWITZ Alan  Department of Pediatrics, Harverd Medical School
REID Kenneth b m  MRC.University of Oxford
Project Period (FY) 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1995: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordscomplement / lectin pathway / MBP / MASP / C1
Research Abstract

Serum mannose-binding protein (MBP) is a C-type lectin capable of activating the complement system (the lectin pathway). A novel serine protease designated MASP (MBP-associated-serine protease) is involved in the activation by MBP,exerting C4-and C2-activating capacity when bound to MBP on its ligands.
1.We investigated reconstitution of recombinant MBPs and MASP for exhibiting complement activation. Wild type recombinant MBP (MBP_G) was found to be able to be associated with MASP,resulting in complement activation, whereas recombinant mutated MBP (MBP_D) in which glycine (G) is substituted with asparatic acid (D) in the fifth collagen repeat and responsible for the complement-dependent opsonic defect is unable to activate complement when incubated with MASP.These results indicate that lack of complement-activating capacity of MBP_D might be due to inability of association with MASP (Biochem.J., 1995).
2.To clarify the mechanisms by which C1r/C1s is substitute for MASP in the activation of the lectin pathway, we measured the affinity constant of C1r/C1s or C1q and MBP using a Biacore apparatus. The results indicate that affinity constants of the four possible mixtures are very similar. Since only MBP-MASP and C1q-C1r/C1s complexes were present in serum, the other factors would influence the interaction of MBP and C1r/C1s.
3.To evaluate the role of the MASP in various diseases, we established sandwich ELISA using several monoclonal antibodies. The mean value of normal human is about 6mug/ml. Estimation of MASP in various diseases is currently under investigation.

Report

(1 results)
  • 1995 Final Research Report Summary
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] M.Matsushita,R.A.B.Ezekowitz,T.Fujita: "TheGly・54→Aspallelicform of human mannosc-binding protein(MBP)fails to bind MBP-associated serine protease" Biochem.J.311. 1021-1023 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] I.Terai,K.Kobayashi,M.MatsushitaT.Fujita,K.Matsuno: "α_2-Maasqloluhin bindsto and inhibits mannose-binding protein-associated serine protease" International Immunology. 7. 1579-1584 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Matsushita,T.Fujita: "Cleavage of the third component of conplement(C3)by mannose-binding protein-associated serine protease(MASP)with subsequent complement activation" Immunobiol.194. 443-448 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Matsushita,T.Fujita: "The lectin pathway of complement activation." Res.Immunol. (in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Matsushita,T.Fujita: "MASP In Collectin'ed by Ezekowitz et al" RG Lndes Co(in press), (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Matsushita, R.A.B.Ezekowitz: "The Gly54*Asp allecic form of human mannose-binding protein (MBP) tails to bind MBP-associated serine protease" Biochem.J.311. 1021-1023 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] I.Terai, K.Kobayashi, M.Matsushita, T.Fujita, K.Matsuo: "alpha_2-Macroglolulin binds to and inhibits mannose-binding protein-associated serine protease" International Immunology. 7. 1579-1584 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Matsushita, T.Fujita: "Cleavage of the third component of complement (C3) by mannose-binding protein-associated serine protease (MASP) with subsequent complement activation" Immunobiol. 194. 443-448 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Matsushita, T.Fujita: "The lectin pathway of Complement activation" Res.Immunol. (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Matushita, T.Fujita: RG Landes co. (in press). MASP.In "Collectin" ed by Ezekowitz et al., (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary

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Published: 1995-04-01   Modified: 2016-04-21  

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