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Analysis of regulation of blood coagulation using functional-blocking monoclonal antibodies

Research Project

Project/Area Number 15591011
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionSaga University (2004)
佐賀医科大学 (2003)

Principal Investigator

FUKUDOME Kenji  Saga University, Medicine, Associate Professor, 医学部, 助教授 (50284625)

Co-Investigator(Kenkyū-buntansha) KIMOTO Masao  Saga University, Medicine, Professor, 医学部, 教授 (40153225)
TSUNEYOSHI Naoko  Saga University, Medicine, Assistant Professor, 医学部, 助手 (80336114)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsthrombosis / endothelial / monoclonal antibody / blood coagulation
Research Abstract

To investigate the molecular mechanism for regulation of blood coagulation, we prepared functional blocking monoclonal antibodies(MAbs) against blood coagulation factors and the relation factors. We established function-blocking MAbs against the endothelial cell protein C receptor(EPCR). As shown in the references, we could demonstrate novel physiological function of EPCR. To collaborate with the thrombin receptor, EPCR mediated signal trunsduction triggered by activated protein C(APC). The signal resulted anti-inflammatory and anti-apoptotic responses in endothelial cells. We also established MAbs against to thrombomodulain, which reacted to each domains in the extracellular region. Analysis with the antibodies demonstrated possibilities of unknown molecular mechanism for protein C activation. The detail analysis for the mechanism is underway. MAbs against mouse prothrombin and antithrombin III were also established. We are trying to establish a sandwich ELISA system for detection of thrombin/ATIII complex in mice. By using these materials, we would like to investigate the molecular mechanism of in vivo regulation of blood coagulation.

Report

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

    (21 results)

All 2005 2004 2003 Other

All Journal Article (15 results) Publications (6 results)

  • [Journal Article] The functional and structural properties of MD-2 required for lipopolysaccharide binding are absent in MD-1.2005

    • Author(s)
      Tsuneyoshi N
    • Journal Title

      J Immunol. 174

      Pages: 340-344

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Activated protein C induces endothelial cell proliferation by mitogen-activated protein kinase activation in vitro and angiogenes is in vivo.2004

    • Author(s)
      Uchiba M
    • Journal Title

      Circ.Res. 95

      Pages: 34-41

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Autoantibodies against EPCR are found in antiphospholipid syndrome and are a risk factor for fetal death.2004

    • Author(s)
      Hurtado V
    • Journal Title

      Blood 104

      Pages: 1369-1374

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Activated protein C inhibits bronchial hyperresponsiveness and Th2 cytokine expression in mice.2004

    • Author(s)
      Yuda H
    • Journal Title

      Blood 103

      Pages: 49-49

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] MD-2のLPS結合におけるヒトとマウスの違い2004

    • Author(s)
      常吉 直子
    • Journal Title

      日本免疫学会総会誌 34

      Pages: 48-48

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] 大腸菌によるCD14の発現と機能解析2004

    • Author(s)
      小原 潤
    • Journal Title

      日本免疫学会総会誌 34

      Pages: 53-53

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Activated protein C induces endothelial cell proliferation by mitogen-activated protein kinase activation in vitro and angiogenesis in vivo.2004

    • Author(s)
      Uchiba M
    • Journal Title

      Circ.Res. 95

      Pages: 34-41

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Activated protein C inhibits the expression of platelet-derived growth factor in the lung.2003

    • Author(s)
      Shimizu S
    • Journal Title

      Am J Respir Crit Care Med. 167

      Pages: 1416-1426

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression and function of the endothelial protein C receptor in human neutrophils2003

    • Author(s)
      Sturn DH
    • Journal Title

      Blood 102

      Pages: 1499-1505

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Activated protein C alters cytosolic calcium flux in human brain endothelium via binding to endothelial protein C receptor and activation of protease activated receptor-1.2003

    • Author(s)
      Domotor E
    • Journal Title

      Blood 101

      Pages: 4797-4801

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective2003

    • Author(s)
      Cheng T
    • Journal Title

      Nat Med 9

      Pages: 338-342

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of MD-1 protein in CHO cells.2003

    • Author(s)
      Tsuneyoshi N
    • Journal Title

      生化学 75

      Pages: 873-873

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] MD-2蛋白の大腸菌での発現2003

    • Author(s)
      福留健司
    • Journal Title

      日本免疫学会総会誌 33

      Pages: 126-126

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Activated protein C inhibits the expression of platelet-derived growth factor in the lung.2003

    • Author(s)
      Shimizu S
    • Journal Title

      Am J Respir Grit Care Med. 167

      Pages: 1416-1426

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of MD-1 protein in CHO cells.2003

    • Author(s)
      Tsuneyoshi N
    • Journal Title

      Seikagaku 75

      Pages: 873-873

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Shimizu S: "Activated protein C inhibits the expression of platelet-derived growth factor in the lung."Am J Respir Crit Care Med.. 167. 1416-1426 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sturn DH: "Expression and function of the endothelial protein C receptor in human neutrophils"Blood. 102. 1499-1505 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Domotor E: "Activated protein C alters cytosolic calcium flux in human brain endothelium via binding to endothelial protein C receptor and activation of protease activated receptor-1."Blood. 101. 4797-4801 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Cheng T: "Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective"Nat Med. 9. 338-342 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsuneyoshi N: "Expression of MD-1 protein in CHO cells."生化学. 75. 873 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 福留健司: "MD-2蛋白の大腸菌での発現"日本免疫学会総会誌. 33. 126 (2003)

    • Related Report
      2003 Annual Research Report

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

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