1988 Fiscal Year Final Research Report Summary
Elucidation of the mechanism of endotoxin-induced disseminated intravascular coagulation; Tissue factor activity in macrophage and granulocyte.
| Project/Area Number |
61570214
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
細菌学
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| Research Institution | Iwate Medical University |
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Principal Investigator |
HIRATA Michimasa Department of Bacteriology, School of Medicine, Iwate Medical University., 医学部, 講師 (20048359)
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| 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)
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| Project Period (FY) |
1986 – 1988
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| Keywords | Endotoxin 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 |
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| 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.
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