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Elucidation of the mechanism of endotoxin-induced disseminated intravascular coagulation; Tissue factor activity in macrophage and granulocyte.

Research Project

Project/Area Number 61570214
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 細菌学
Research InstitutionIwate Medical University

Principal Investigator

HIRATA Michimasa  Department of Bacteriology, School of Medicine, Iwate Medical University., 医学部, 講師 (20048359)

Co-Investigator(Kenkyū-buntansha) TSUNODA Nobuko  Department of Bacteriology, School of Medicine, Iwate Medical University., 医学部, 助手 (90128926)
YOSHIDA Masao  Department of Bacteriology, School of Medicine, Iwate Medical University., 医学部, 教授 (50048229)
Project Period (FY) 1986 – 1988
Project Status Completed (Fiscal Year 1988)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1988: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1987: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1986: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsEndotoxin shock / Disseminated intravascular coagulation / Tissue factor / Endotoxin-binding cationic protein / antibacterial activity / anticoagulant activity / Macrophage / マクロファージ / 腫瘍壊死因子 / ニホンザル / 顆粒球 / 白血球動態 / 播種性血管内凝固 / フィブロネクチン / 内毒素
Research Abstract

1. Tissue factor(TF). 1) By prior incubation of TF with fibronectin(FN), about 50 to 80 % of the TF activity was inhibited. 2) FN also inhibited the TF activity of bone marrow cells from mouse given endotoxin. 3) TF-induced lethality in mice was inhibited by preincubation of TF with FN. Inhibitory effect of FN on the TF activity is thought to be due to the binding of FN to phospholipid portion of TF. In Japanese monkey, 1) Endotoxin(LPS) induced a fever around 0.5 to 1.0 C that peaked at 1 hr. 2) LPS induced leukopenis 30 min after injection then followed by leukocytosis. 3) TF activities of monomuclear cell and granulocyte obtained from peripheral blood, spleen and bone marrow increased significantly compared to control 12 hr after LPS. 4) Plasma TNF(tumor necrosis factor) increased 0.5 to 1 hr after LPS to peak concentration of 250 to 390 pg/ml. 5) No increase in plasma IL-1 was observed during 12 hr. These indicate that TNF/cachectin released after LPS administration is thought to be a primary mediator responsible for initiation of these biological activities of LPS. 2. Cationic proteins(CAP). 1) CAP from rabbit granulocytes agglutinated sheep, human and mous erythrocvtes sensitized with LPS. (2) CAP prolonged the clotting time of human plasma. 3) Anticoagulant property rsulted from inhibition of factor Xa or prothrombinase formation. 4) CAP showed antibacterial activity to S. typhimurium, S. minnesota and also to S. aureus. 5) LPS-binding, anticoagulant and antibacterial activities were absorbed by prior incubation of CAP with LPS or heparin. 6) By gel filtration, two fractions had LOS-binding activities and the molecular weights were around 68K and 10K. These finding suggest that DIC( disseminated intravascular coagulation) manifestation in endotoxemia, due to gram negative bacterial infections, are controlled by CAP released from granulocytes.

Report

(4 results)
  • 1988 Annual Research Report   Final Research Report Summary
  • 1987 Annual Research Report
  • 1986 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] M.Hirata;N.Tsunoda;K.Inada;M.Yoshida: J.Immunol.Immunopharmacology.VI. 171 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 平田陸正、角田伸子、吉田昌男: 血液と脈管. 18. 486-488 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 角田伸子、平田陸正、吉田昌男: 血液と脈管. 18. 592-594 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 平田陸正、中村伸、後藤俊二、川崎一、田村弘志、田中重則、吉田昌男: 毒素シンポジウム予稿集. 35. 125-129 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 平田陸正: 代謝. 26. (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] M.Hirata;M.Yoshida;K.Inada;T.Kirikae: International Symposium on Endotoxin. (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] M.Hirata; N.Tsunoda; K.Inada; M.Yoshida: "Agglutination of eruthrocytes sensitized with Re-LPS elicited by cationic protein from rabbit granulocytes." J. Immunol. Immunopharmacol. VI. 171 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] N.Tsunoda; M. Hirata; M.Yoshida: "Endotoxemia and tissue thromboplastin activity in the bone marrow cells; Effects of fibronectin." Blood and Vessel. 18. 486-488 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] M.Hirata; N.Tsunoda; M.Yoshida: "Anticoagulant, cationic protein(CAP) isolated from granulocytes; Endotoxin-binding property of CAP." Blood and Vessel. 18. 592-594 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] M.Hirata; M.Yoshida; K.Inada; T.Kirikae: "Investigation of endotoxin binding cationic proteins from granulocytes; Agglutination of erythrocytes sensitized with Re-LPS." International Symposium on Endotoxin. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] M.Hirata: "Entotoxin and blood coagulation" Metabolism and Disease. 26. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 平田陸正,下村有子,稲田捷也,吉田昌男: 血液と脈管. 19. 465 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 平田陸正,角田伸子,稲田捷也,吉田昌男: 日本細菌学雑誌. 43. 141 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 平田陸正,中村伸,後藤俊二,川崎一,田村弘志,田巾重則,吉田昌男: 毒素シンポジウム予稿集. 35. 125-129 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 平田陸正: 代謝. 26. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] M.Hirata;M.Yoshida;K.Inada;T.Kirikae: International Symposium on Endotoxin. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 平田陸正, 吉田昌男: 日本細菌学雑誌. 42. 431 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 角田伸子, 平田陸正, 吉田昌男: 日本細菌学雑誌. 42. 425 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 角田伸子, 平田陸正, 吉田昌男: 血液と脈管. 18. 486-488 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 平田陸正, 角田伸子, 吉田昌男: 血液と脈管. 18. 592-594 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 平田陸正, 角田伸子, 稲田捷也, 吉田昌男: 日本細菌学雑誌. 43. 141 (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] M.Hirata;N.Tsunoda;K.Inada;M.Yoshida: J.Immunol.Immunopharmacology. 【VI】. 171 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 平田陸正,角田伸子,稲田捷也,吉田昌男: 第33回毒素シンポジウム予講集. 33. 134-139 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 角田伸子,平田陸正,吉田昌男: 血液と脈管. (1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] 平田陸正,角田伸子,吉田昌男: 血液と脈管. (1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] 平田陸正,吉田昌男: 日本細菌学雑誌. 42. 431 (1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] 角田伸子,平田陸正,吉田昌男: 日本細菌学雑誌. 42. 425 (1987)

    • Related Report
      1986 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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