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Inhibitotory Effect of Cathepsin B Inhibitor CA 074 on Xenograft Rejection

Research Project

Project/Area Number 12671161
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionEhime University

Principal Investigator

KIYOCHI Hidenori  Ehime University Hospital, Instructor, 医学部附属病院, 助手 (00314956)

Co-Investigator(Kenkyū-buntansha) KOBAYASHI Nobuaki  Ehime University, Faculty of Medicine, Professor, 医学部, 教授 (60135564)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥3,200,000 (Direct Cost: ¥3,200,000)
Keywordscathepsin B inhibitor / xenotransplantation / indirect recognition / CA074 / mixed lymphocyte reaction / antigen processin / 間接抗原認識 / 移植 / 異種 / プロテアーゼ / リンパ球培養 / カテプシン / 抗原提示 / マウス
Research Abstract

Due to species disparities, direct cellular interaction between donor antigen-presenting cells (APC) and recipient T lymphocytes is not strong in xenotransplantation. Indirect recognition, in which recipient T cells recognized processed donor antigens on the MHC class II cell surface molecules of recipient self APC, appears more significant than direct recognition in xenoantigen recognition. Cathepsin B is one of the determinant protease responsible for foreign antigen processing by APC. CA074 reported to be a potent specific inhibitor of cathepsin B. In the present study, immunosuppressive effect of cathepsin B inhibitor CA074 on indirect xeno-antigen recognition was investigated.
One way mixed lymphocyte reaction (MLR) was performed in rat-to-mouse combination. B cell depleted B6 mouse splenocytes (2 x 10^5), including T cell and APC population, were used as responder. Irradiated (3000 rad) F344 rat erythrocytes (40 x 10^5) and splenocytes (4 x 10^5) were used for 'indirect' (Ind-MLR) and 'direct plus indirect' (Both-MLR) stimulation, respectively. CA074 100 mg/ml concentration suppressed xenogenic erythrocyte stimulated MLR (Ind-MLR), which is evoked by exclusively indirect recognition, to the control level. Xenogenic splenocyte stimulated MLR (Both-MLR), which include direct and indirect recognition was partially suppressed by CA074. By adding various concentrations, from 10 to 100 mg/ml, of CA074 to the culture, a dose-dependent inhibition was observed in Ind-MLR, and mitogenic responses by ConA were not affected by CA074. In conclusion, CA074 suppressed indirect xeno-antigen recognition on rat-to-mouse MLR by blocking the donor antigen processing in recipient APC. It will be a novel strategy for immunosuppression of xeno cellular response.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] Tohyama T: "Inhibitotory effect of Cathepsin B inhibitor CA 074 on mouse anti-rat mixed lymphocyte reaction : Novel immunosuppressive strategy for indirect xenoantigen recognition"Transplantation Proceedings. 32. 944-945

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tohyama T., Kiyochi H., Narumoto K., Kobayashi N., Kanoh M., Saibara T., Katunuma N.: "Inhibitotory effect of Cathepsin B inhibitor CA 074 on mouse anti-rat mixed lymphocyte reaction: Novel immunosuppressive strategy for indirect xenoantigen recognition"Transplantation Proceedings. 32. 944-945 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tohyama T: "Inhibitotory effect of Cathepsin B inhibitor CA 074 on mouse anti-rat mixed lymphocyte reaction : Novel immunosuppressive strategy for indirect xenoantigen recognition"Transplantation Proceedings. 32. 944-945 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Taiji Tohyama: "Inhibitory effect of Cathepsin B inhibitor CA074 on mouse anti-rat mixed lymphocyte reaction."Transplantation Proceedings. 32. 944-945 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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