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Development of effective inhibitors against carbohydrate recognition adhesion molecules involved in invasion of inflammatory cells and/or cancer cells.

Research Project

Project/Area Number 08557025
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Immunology
Research InstitutionOsaka University

Principal Investigator

MIYASAKA Masayuki  Osaka University Medical School, Professor, 医学部, 教授 (50064613)

Co-Investigator(Kenkyū-buntansha) NAKADE Shinji  Ono Pharmaceutical Co.Ltd, Basic Research Institute, Investigator, 基礎研究所, 研究員
FUKUSHIMA Daikichi  Ono Pharmaceutical Co.Ltd, Basic Research Institute, Director, 基礎研究所, 所長
SUZUKI Yasuo  University of Shizuoka, School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (00046278)
KAWASHIMA Hiroto  Osaka University Medical School, Assistant Professor, 医学部, 助手 (50260336)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥12,200,000 (Direct Cost: ¥12,200,000)
Fiscal Year 1997: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1996: ¥7,200,000 (Direct Cost: ¥7,200,000)
Keywordsselectin / CD44 / proteoglycan / versican / anti-inflammatory agent / leukocyte / acute inflammation / adhesion molecules / 抗炎症剤
Research Abstract

1. We have for the first time succeeded in identifying versican as a ligand for a leukocyte adhesion molecule, L-selectin. Versican is a large chondrotin sulfate proteoglycan produced by fibroblasts. Unlike other ligands for L-selectin, versican is not modified with sialyl Lewis X type carbohydrates, but has chondroitin sulfate side chains which interacts with the lectin domain of L-selectin. Versican is localized in epithelial cells of distal tubules of the kidney under physiological conditions, but is rapidly released from there under pathological conditions. The shed versican is then recognized by leukocyte L-selectin, which may promote tissue injury.
2. Versican can bind to not only L-selectin but also other inflammatory adhesion molecules, such as P-selectin and CD44. In addition, it can capture a certain type of chemokines on its chondrotin sulfate side chains, which may result in augmenting inflammatory responses. It was revealed that functional inhibition of L-selectin leads to inhibition of interstitial nephritis induced by ureteral obstruction.
3. We have found a substance that can inhibit fucosylation and sialylation of cell surface proteins.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Mulligan, M.S.et al.: "Protective effects of combined adhesion molecule blockade in models of acute lung injury." Proc.Assoc.Amer.Physicians. 108. 198-208 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kawashima, H.et al.: "Characterization of a 180 kDa molecule apparently reactive with recombinant L-selectin." Glycoconjugate J.14. 321-330 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ishiwatari-Hayasaka, H.et al.: "Induction of cell death by chimeric L-selectin-Fas receptors." Int.Immunol.9. 627-635 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miyasaka, M.et al.: "Involvement of selectins in atherogenesis : A primary or secondary event?" Ann.N.Y.Acad.Sci.811. 25-35 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ding, Z.et al.: "A sulfatide receptor distinct from L-selectin is involved in lymphocyte activation" FEBS Letters. 418. 310-314 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Toyama-Sorimachi, N.et al.: "Widespread expression of chondroitin sulfate-type serglycins with CD44 binding ability in hemopoietic cells" J.Biol.Chem.272. 26714-26719 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miyasaka, M.: "Selectins (CD62-E/L/P)" Encyclopedia of Immunology P.J.Delves & I.Roitt. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mulligan, M.S.et al.: "Protective effects of combined adhesion molecule blockade in models of acute lung injury." Proc.Assoc.Amer.Physicians. 108. 198-208 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kawashima, H.et al.: "Characterization of a 180kDa molecule apparently reactive with recombinant L-selectin." Glycoconjugate J.14. 321-330 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ishiwatari-Hayasaka, H.et al.: "Induction of cell death by chimeric L-selectin-Fas receptors." Int.Immunol.9. 627-635 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miyasaka, M.et al.: "Involvement of selectins in atherogenesis : A primary or secondary event?" Ann.N.Y.Acad.Sci.811. 25-35 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ding, Z.et al.: "A sulfatide receptor distinct from L-selectin is involved in lymphocyte activation" FEBS Letters. 418. 310-314 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Toyama-Sorimachi, N.et al.: "Widespread expression of chondroitin sulfate-type serglycins with CD44 binding ability in hemopoietic cells" J.Biol.Chem.272. 26714-26719 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miyasaka, M.: "Selectins (CD62-E/L/P)" Encyclopedia of Immunology, P.J.Delves & I.Roitt. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mulligan,M.S.et al.: "Protective effects of combined adhesion molecule blockade in models of acute lung injury." Proc.Assoc.Amer.Physicians. 108. 198-208 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kawashima,H.et al.: "Characterization of a 180 kDa molecule apparently reactive with recombinant L-selectin." Glycoconjugate J.14. 321-330 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ishiwatari-Hayasaka,H, et al.: "Induction of cell death by chimeric L-selectin-Fas receptors." Int.Immunol.9. 627-635 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Miyasaka,M.et al.: "Involvement of selectins in atherogenesis:A primary or secondary event?" Ann.N.Y.Acad.Sci.811. 25-35 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ding.Z.et al.: "A sulfatide receptor distinct from L-selectin is involved in lymphocyte activation" FEBS Letters. 418. 310-314 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Toyama-Sorimachi,N.et al.: "Widespread expression of chondroitin sulfate-type serglycins with CD44 binding ability in hemopoietic cells" J.Biol.Chem.272. 26714-26719 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Miyasaka,M.: "Encyclopedia of Immunology (P.J.Delves & I.Roitt.ed.)" Selectins (CD62-E/L/P),(in press),

    • Related Report
      1997 Annual Research Report
  • [Publications] Mulligan,M.S.: "Protective effects of combined adhesion molecule blockade in models of acute lung injury." Proc.Assoc.Amer.Physicians. 108. 198-208 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kurose,I.: "Microvascular dysfunction induced by nonsteroidal anti-inflammatory drugs:role of leukocytes." Am.J.Physiol.270. G363-G369 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Horie,Y.: "Leukocyte adhesion and hepatic microvascular responses to intestinal ischemia/reperfusion in rats." Gastroenterology. 111. 666-673 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ishiwatari-Hayasaka,H.: "Induction of cell death by chimeric L-selectin-Fas receptors." Int.Immunol.(in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Kawashima,H.: "Characterization of a 180 kDa molecule apparently reactive with recombinant L-selectin." Glycoconjugate J.(in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Miyasaka,M.: "Involvement of selectins in atherogenesis-A primary or secondary event?" Ann.N.Y.Acad.Sci.(in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Miyasaka,M.: "Encyclopedia of Immunology(Selectins(CD62-E/L/P)" (in press)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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