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Mechanisms of pyknotic cell death in vivo and their biological significance

Research Project

Project/Area Number 10470002
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General anatomy (including Histology/Embryology)
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

ITOH Tsunetoshi  School of medicine, Tohoku Univ., Professor, 大学院・医学系研究科, 教授 (90004746)

Co-Investigator(Kenkyū-buntansha) SOGA Hiroyuki  School of medicine, Tohoku Univ., Research Associate, 大学院・医学系研究科, 助手 (20282121)
YAGI Hideki  School of medicine, Tohoku Univ., Research Associate, 大学院・医学系研究科, 助手 (40250740)
NAKAMURA Masanori  School of medicine, Tohoku Univ., Associate Professor, 大学院・医学系研究科, 助教授 (50180394)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1999: ¥3,900,000 (Direct Cost: ¥3,900,000)
KeywordsThymus / Thymocytes / Differentiation / Selection / Clonal deletion / Microenvironment / Apoptosis / Cell death
Research Abstract

Most of programmed cell deaths during the developmental processes have been considered to be apoptosis accompanying DNA fragmentation. We have precisely examined thymocyte deaths and B cell deaths in the germinal centers, i.e., "cell deaths" in situ, and found that they are pyknosis with heavy nuclear condensation without DNA fragmentation ; they are totally distinct from typical apoptosis, which is characterized by DNA fragmentation and marginal chromatin condensation. We re-evaluated various cell deaths in vivo, and rectategorize those in situ cell deaths on the basis of the novel point of view, in order to analyze the mechanisms of the new type of cell deaths, pyknosis, and to delineate their biological significance.
We analyzed morphologically cell deaths in vivo during the development, especially the cell deaths observed in the interdigital tissues and found that the cell deaths in this tissue did not accompany DNA fragmentation, and accordingly, we concluded that they are not apoptosis. Massive cell deaths triggered by anti-CD3 antibody treatment have been found typical apoptosis, because they fragmented DNA at much earlier stages when morphological changes could be observed.
We have undertaken a project to develop a monoclonal antibody to detect the earliest sign of pyknosis, a surface antigen of dying thymocytes to be recognized by macrophages for ingestion. This project has been underway, and will be pursued until the development of the antigen.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Itoh T.et al.: "Thymocyte and B-cell death without DNA fragmentation"Handb. Exp. Pharmacol.. 142. 375-397 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamura M.et al.: "A time kinetic study of the effect of aminobisphosphonate on murine haemopoiesis"British J. Haematol.. 107. 779-790 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohtsu S.et al.: "Enhanced neutrophilic granulopoiesis in rheumatoid arthritis"J. Rheumatol.. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yagi H.et al.: "Immunosuppressant FTY720 inhibits thymocyte emigration"Eur. J. Immunol.. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 伊藤恒敏他: "胸腺・リンパ節 in 「臓器別アポトーシス証明法」"南江堂. (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamura, M., Yagi, H., Endo, Y., Kosugi, Y., Ishii, T., and Itoh, T.: "A time kinetic study of the effect of aminobisphosphonate on murine haemopoiesis"British J. Haematol. 107. 779-790 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yagi, H., Kamba, R., Chiba, K., Soga, H., Yaguchi, K., Nakamura, M., and Itoh, T.: "Immunosuppressant FTY720 inhibits thymocyte emigration"Eur. J. Immunol.. 30 (In press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohtsu, S., Yagi, H., Nakamura, M., Isii, T., Kayaba, S., Soga, H., Gotoh, T., Rikimaru, A., Kokubun, S., and Itoh, T.: "Enhanced neutrophilic granulopoiesis in rheumatoid arthritis. Involvement of neutrophils in desease progression."J. Rheumatol. 2000. (In press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsunetoshi Itoh, M. Nakamura, Y. Yagi, H. Soga, and T. Ishii: "Thymocyte and B-cell death without DNA fragmentation."In Apoptosis and Its Modulation by Drugs (Ed. R.G. Cameron and G. Feuer), Springer. (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kayaba, S., Nakamura, M., Yagi, H., Soga, H., Ogata, M., Ishii, T., Gotoh, T., Ohtsu, S., Kasahara, S., Doi, H., Satomi, S., Ohara, S., Toyota, T., and Itoh, T.: "Simulation of intraepithelial lymphocytes via TCR trigers rapid and extensive apoptosis of epithelial cells of the jejunum and causes severe diarrhea."Cell Tiss. Res.. (In submission).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Gotoh, T., Nakamur, M., Soga, H., Yagi, H., Ishii, T., Kayaba, S., Yamad, A., and Itoh, T.: "Immunohistochemical and ultrastructural analysis of the programmed cell death and phagocytes in the developing interdigital region of the fetal mouse limb bud."Anat. Embryol.. (In submission).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Soga, H., Nakamura, M., Yagi, H., and Itoh, T.: "Differences in the phagocytotic capability in situ among mouse thymic macrophage subsets."Cell Tiss. Res.. (In submission).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsunetoshi Itoh, M. Nakamura, Y. Yagi and H. Soga: "The thymus. They lymph nodes. In Detection methods in different organs and tissues. (Ed. K. Ohtsuki, T. Kohji, and K. Watanabe)(In Japanese)"Nankodo, Japan. (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Itoh T.et al.: "Thymocyte and B-cell death without DNA fragmentation"Handb. Exp. Pharmacol.. 142. 375-397 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakamura M.et al.: "A time kinetic study of the effect of aminobisphosphonate on murine haemopoiesis"British J. Haematol.. 107. 779-790 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ohtsu S.et al.: "Enhanced neutrophilic granulopoiesis in rheumatoid arthritis"J. Rheumatol.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yagi H.et al.: "Immunosuppressant FTY720 inhibits thymocyte emigration"Eur. J. Immunol.. (in ptess). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 伊藤 恒敏 他: "胸腺・リンパ節 in 「臓器別アポトーシス証明法」"南江堂. (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Itoh,T,et al: "Thymocyte and B-cell death without DNA frogmentation" Apoptosis and its modulation by drugs. (in press). (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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