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Development of anti-inflammatory drugs affecting functions of platelet adhesion molecules

Research Project

Project/Area Number 06557134
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section試験
Research Field 医薬分子機能学
Research InstitutionUniversity of Tokyo

Principal Investigator

TSUJI Tsutomu  University of Tokyo, Associate Professor, 薬学部, 助教授 (00143503)

Co-Investigator(Kenkyū-buntansha) MASUDA Jun-ishi  Shimane Medical University, Professor, 医学部, 教授 (70173747)
YAMAMOTO Kazuo  University of Tokyo, Assistant Professor, 薬学部, 助手 (20174782)
IMAI Yasuyuki  University of Tokyo, Assistant Professor, 薬学部, 助手 (80160034)
IRIMURA Tatsuro  University of Tokyo, Professor, 薬学部, 教授 (80092146)
Project Period (FY) 1994 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 1996: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1995: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1994: ¥4,000,000 (Direct Cost: ¥4,000,000)
KeywordsPLATELET / LEUKOCYTE / CELL ADHESION / INFLAMMATION / OXYGEN RADICAL / CYTOKINE / SELECTIN / CARBOHYDRATE CHAIN / TNF / スーパーオキシド
Research Abstract

The purpose of this research project was the establishment of the basic concepts of the development of anti-inflammatory drugs affecting the cell adhesion between blood platelets and leukocytes. We got the following results.
(1) The screening methods of anti-platelet drugs modifying the functions of platelet adhesion molecules have been developped, where we utilized flow cytometry with fluorescence-labeled platelets and unlabeled leukocytes (2) Recombinant soluble P-selectin inhibited the superoxide anion production in leukocytes stimulated by formyl peptides or tumor necrosis factor-alpha (TNF-alpha). However, the soluble P-selectin had no effect on the oxygen radical production in these cells stimulated by phorbor ester or arachidonic acid. (3) The Neutrophils pretreated with interleukin-8 produced the oxygen radical in response to the soluble P-selectin. (4) When monocytes derived from peripheral blood were incubated in a plate which had been coated with P-selectin, these cells produced TNF-alpha. The optimal concentration of P-selectin for the coating of the plates was found to be 0.3 mug/ml. (5) When leukocytes were incubated with immobilized P-selectin, they peoduced superoxide anion and TNF-alpha. The distribution of P-selectin ligand, sialyl Lewis X carbohydrate, on these cells was examined by immuno-fluorescence microscopy. This carbohydrate epitopes were found to form a cluster at the bottom of the cell, which is the attachment site to the plate. This observation suggested the possible relationship between the leukocyte activation by P-selectin and the cluster formation of its carbohydrate ligand.

Report

(4 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Tsuji,T et al.: "Induction of superoxide anion production from monocytes and neutrophils by activated platelets through the P-selectin-sialy Lewis X interaction." Journal of Leukocyte Biology. 56. 583-587 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nagata,K et al.: "Role of O-linked carbohydrate chains on leukocyte cell membranes in platelet-induced leukocyte activation." Journal of Biological Chemistry. 269. 23290-23295 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Suzuki,K et al.: "Activation induces dephosphorylation of cofilin and its translocation to plasma membranes in neutrophil-like differentiated HL-60 cells." Journal of Biological Chemistry. 270. 19551-19556 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tsuji T,Nagata K,Koike J,Todoroki N,Irimura T.: "Induction of superoxide anion production from monocytes and neutrophils by activated platelets through the P-selectin-sialy Lewis X interaction." J Leukocyte Biol. 56. 583-587 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nagata, K,Tsuji T,Hanai N,Irimura T.: "Role of O-linked carbohydrate chains on leukocyte cell membranes in platelet-induced leukocyte activation." J Biol Chem. 269. 23290-23295 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Suzuki K,Yamaguchi T,Tanaka T,Kawanishi T,Nishimaki-Mogami T,Yamamoto K,Tsuji T, Irimura T,Hayakawa T,Takahashi A.: "Activation induces dephosphorylation of cofilin and its translocation to plasma membranes in neutrophil-like differentiated HL-60 cells." J Biol Chem. 270. 19551-19556 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 辻 勉: "セレクチンと炎症反応" 臨床免疫. 28巻7号. 859-868 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K. Suzuki 他: "Activation induces dephosphorylation of cofilin and its trauslocation to plasma membranes in neutrophil-like HL-60 cells" Journal of Biological Chemistry. 270. 19551-19556 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 辻勉: "セレクチンと炎症反応" 臨床免疫. 28(印刷中). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] K.Nagata: "Role of O-linked carbohydrate chains on leukocyte cell membranes in plateiet-induced leukocyte activation" Journal of Biological Chemistry. 269. 23290-23295 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Tsuji: "Induction of superoxide anion production from monocytes and neutrophils by activated platelets through P-selectin-" Sournal of Leukocyte Biology. 56. 583-587 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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