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

1.组织因子（TF）。1)通过预先将TF与纤连蛋白（FN）孵育，约50 - 80%的TF活性被抑制。2)FN对内毒素诱导的小鼠骨髓细胞TF活性也有抑制作用。3)TF诱导的小鼠致死率被TF与FN预孵育抑制。FN对TF活性的抑制作用被认为是由于FN与TF的磷脂部分结合。在日本猴中，1）内毒素（LPS）在0.5 - 1.0 ℃左右引起发热，在1小时达到高峰。2）LPS在注射后30分钟引起白细胞减少，然后是白细胞增多。3)LPS刺激后12小时，外周血、脾和骨髓单核细胞和粒细胞TF活性均显著高于对照组。4)血浆TNF（肿瘤坏死因子）在LPS后0.5至1小时增加至250至390 pg/ml的峰值浓度。5)在12小时内没有观察到血浆IL-1的增加。这些表明，LPS给药后释放的TNF/cachectin被认为是负责启动LPS这些生物活性的主要介质。2.阳离子蛋白（CAP）。1)兔粒细胞CAP能凝集LPS致敏的绵羊、人和小鼠红细胞。(2)CAP延长人血浆凝血时间。3)抗凝血特性是由于抑制凝血因子Xa或凝血酶原酶的形成。4)CAP对S.鼠伤寒沙门氏菌（S. miniaturia和S.金黄色。5)LPS结合，抗凝血和抗菌活性被吸收的前孵育的CAP与LPS或肝素。6)凝胶过滤结果表明，两个组分具有LOS结合活性，分子量分别为68K和10K。这些发现表明，由于革兰氏阴性细菌感染引起的内毒素血症的弥散性血管内凝血（DIC）表现是由粒细胞释放的CAP控制的。

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.