GENERATION IN PLASMA OF A FAST-ACTING INHIBITOR OF PLASMINOGEN-ACTIVATOR IN RESPONSE TO ENDOTOXIN STIMULATION
GENERATION IN PLASMA OF A FAST-ACTING INHIBITOR OF PLASMINOGEN-ACTIVATOR IN RESPONSE TO ENDOTOXIN STIMULATION
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DOI：
10.1172/jci111777
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发表时间：
1985-01-01
影响因子：
15.9
通讯作者：
COLLEN, D
中科院分区：
文献类型：
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作者：
COLUCCI, M;PARAMO, JA;COLLEN, D
产内毒素细菌引起弥散性血管内凝血（DIC）；然而，内毒素在人体中的作用机制尚不清楚。纤维蛋白溶解系统的损伤被认为是一种促进机制。家兔单次注射大肠杆菌脂多糖可使血浆中一种快速作用的纤溶酶原激活物（PA-inhibitor）的水平从3.9。0.7 - 41 .+-。3 h后13.2 U/ml)。凝胶过滤研究表明，兔血浆对人组织型纤溶酶原激活剂（t-PA）的抑制作用伴随着激活剂洗脱谱的变化，这与酶抑制剂复合物的形成相兼容，表观分子量为100,000。在内毒素处理过的动物体内注射人t-PA （1500 IU/kg体重量），可以非常快速地抑制t-PA，并获得类似复合物的信息。循环pa抑制剂活性在家兔体内的半衰期约为。根据供体受体血浆输血实验估计为7分钟。用内毒素刺激培养的人内皮细胞导致pa抑制剂活性在培养基中的积累率提高（增加2至7倍）。在5例败血症患者中，pa -抑制剂水平显著升高(14.3 +-。15.5 U/ml)，与对照组(1.3。0.7 U /毫升)。在所有情况下，t-PA的抑制与尿激酶的抑制之间存在很强的相关性（r = 0.98），这表明这种速效抑制剂与两种纤溶酶原激活剂都有反应。这种速效pa抑制剂的出现对内毒素刺激非常敏感。血中pa抑制剂水平的显著升高可能参与败血症DIC的发病机制。
Endotoxin-producing bacteria cause disseminated intravascular coagulation (DIC); however, the mechanism of endotoxin action in man is still unclear. Impairment of the fibrinolytic system was suggested as a contributing mechanism. A single injection of Escherichia coli lipopolysaccharide in rabbits resulted in a marked and prolonged increase of the levels of a fast-acting inhibitor of plasminogen activator (PA-inhibitor) in plasma (from 3.9 .+-. 0.7 - 41 .+-. 13.2 U/ml after 3 h). Gel filtration studies indicated that inhibition of human tissue-type plasminogen activator (t-PA) by rabbit plasma is accompanied by a change in the elution profile of the activator which is compatible with the formation of an enzyme-inhibitor complex with an apparent MW of 100,000. Injection of human t-PA (1,500 IU/kg body wt.) in endotoxin-treated animals resulted in very fast inhibition of t-PA, and information of a similar complex. The half-life of circulating PA-inhibitor activity in rabbits was .apprx. 7 min, as estimated by donor receiver plasma transfusion experiments. Stimulation of cultured human endothelial cells with endotoxin resulted in an enhanced rate of accumulation of PA-inhibitor activity in the culture medium (2-to 7-fold increase). In 5 patients with septicemia, markedly increased levels of PA-inhibitor (14.3 .+-. 15.5 U/ml) were observed in plasma, as compared with control subjects (1.3 .+-. 0.7 U/ml). A very stong correlation (r = 0.98) was found between inhibition of t-PA and of urokinase in all conditions, suggesting that this fast-acting inhibitor reacts with both plasminogen activators. The appearance of this fast-acting PA-inhibitor is very sensitive to endotoxin stimulation. The marked increase in the level of PA-inhibitor in blood may contribute to the pathogenesis of DIC in septicemia.