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Identification of FX-activating molecules of convulsion-inducing lipoprotein purified from egg granulomas in Schistosoma mansoni-infected mice and of its inducing mechanism

Research Project

Project/Area Number 15590374
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Parasitology (including Sanitary zoology)
Research InstitutionKeio University

Principal Investigator

TANABE Masanobu  Keio University, Department of Tropical Medicine and Parasitology, Assistant Professor, 医学部, 専任講師 (80051928)

Co-Investigator(Kenkyū-buntansha) NAGATA Hiroshi  Keio University, Department of Medicine, Associate Professor, 医学部, 助教授 (00146599)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsSchistosoma mansoni / Egg granulomas / FX-activatina procoagulant / Convulsion-inducing lipoprotein(CILIP) / TLR ligands / SWAP antigen / Signal transduction / マンソン住血吸虫 / 凝固活性化リポ蛋白 / 誘導機構 / シグナル伝達機構 / 虫卵性肉芽腫 / 組織因子 / 凝固第X因子 / 中卵性肉芽腫 / 凝固活性化因子(CILIP) / モノクロナル抗体 / マクロファージ / リンパ球
Research Abstract

Biochemical studies has been performed to identify the factor-X(FX)-activating molecules of convulsion-inducing lipoprotein (CILIP) purified from hepatic egg granulomas in Schistosoma mansoni-infected mice, the inducing mechanism of CILIP by macrophages and dendritic cells, and the signal transduction pathway involved in CILIP induction.
1.In vitro analysis demonstrated that macrophages and dendritic cells could produce CILIP(≒FX-activating PCA) when stimulated with several ligands for Toll-like receptors such as LPS, LTA, peptidoglycan, poly IC and CpGDNA, with splenic DX5+ NK cells and/or CD4+ T cell sensitized with SWAP antigen, or with cytokines such as IFNγ and GM-CSF.
2.The induction of macrophage FX-activating PCA by stimulation with SWAP sensitized lymphocytes required de novo RNA and protein synthesis and activation of PTK and PKC, but not MAPK activation, calmodulin or increase of intracellular Ca++ concentration. Moreover, the induction of macrophage FX-activating PCAwas down-regulated by increment of intracellular cAMP.
3.Two kinds of monoclonal antibodies against CILIP were prepared from BALB/c mice and Wister rats. Rat's MoAb appeared to be highly specific and sensitive to native CILIP, and inhibited dose-dependently FX-activating activity of CILIP, but did not react with denatured CILIP treated with detergents. Sandwich ELISA system using two kinds of MoAbs against CILIP was developed and confirmed its usefulness when applied for quantitative determination of CILIP.
4.Although various biochemical analysis using MoAb against tissue factor and specific antibodies against various coagulation factors have been conducted to identify the EX-activating molecules of CILIP, conclusive evidence has not been obtained yet.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (8 results)

All 2003 Other

All Journal Article (6 results) Publications (2 results)

  • [Journal Article] P13K and negative regulation of TLR signaling.2003

    • Author(s)
      Fukao T, Tanabe M, Terauchi Y, Kadowaki T, Takeuchi T, Koyasu S.
    • Journal Title

      Proceedings of Annual Conference of International Cytokine Society

      Pages: 20-24

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Haemostatic abnormalities in schistosomiasis mansoni.2003

    • Author(s)
      Tanabe M
    • Journal Title

      Parasitology International 52

      Pages: 351-359

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mucosal T cells expressing high levels of IL-7 receptor are potential targets for treatment of chronic colitis.2003

    • Author(s)
      Yamazaki M, Yajima T, Tanabe M, et al.
    • Journal Title

      Journal of Immunology 171

      Pages: 1556-1563

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Haemostatic abnormalities in schistosomiasis mansoni.2003

    • Author(s)
      M.Tanabe.
    • Journal Title

      Parasitology International 52(4)

      Pages: 351-359

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mucosal T cells expressing high levels of IL-7 receptor are potential targets for treatment of chronic colitis.2003

    • Author(s)
      Yamazaki M, Yajima T, Tanabe M, Fukui K, Okada E, Okamoto R, Oshima S, Nakamura T, Kanai T, Uehira M, Takeuchi T, Ishikawa H, Hibi T, Watanabe M.
    • Journal Title

      Journal of Immunology 171(3)

      Pages: 1556-1563

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] PI3K and negative regulation of TLR signaling.

    • Author(s)
      T.Fukao, Masanobu Tanabe, Yasuo Terauchi, Takashi Kadowaki, Tsutomu Takeuchi, Shigeo Koyasu.
    • Journal Title

      Proceedings of Annual Conference of International Cytokine Society on 2003

      Pages: 20-24

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Tanabe M.: "Haemostatic abnormalities in schistosomiasis mansoni"Parasitology International. 52(4). 351-359 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamazaki M, Yajima T, Tanabe M, Fukui K, et al.: "Mucosal T cells expressing high levels of IL-7 receptor are potential targets for treatment of chronic colitis."J.Immunol. 171(3). 1556-1563 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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