Increased plasminogen activator (urokinase) in tissue culture after fibrin deposition.
Increased plasminogen activator (urokinase) in tissue culture after fibrin deposition.
复制标题
纤维蛋白沉积后组织培养物中纤溶酶原激活剂（尿激酶）增加。
DOI：
10.1172/jci107246
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发表时间：
1973
期刊：
影响因子：
--
通讯作者：
M. Bernik
中科院分区：
文献类型：
--
作者：
M. Bernik
纤维蛋白在组织培养中的溶解已被证明是由于纤溶酶原激活剂在免疫学上被鉴定为尿激酶。本研究检查了培养物中的纤溶事件，特别是导致尿激酶水平升高和加速纤溶的机制。在培养的细胞上沉积纤维蛋白之后，培养上清液中尿激酶的含量增加了两到六倍，纤维蛋白迅速消失。对可能导致这些事件的因素(包括纤维蛋白、纤维蛋白原、血管活性刺激以及凝血酶和纤溶酶)的研究表明，尿激酶产量的增加是通过纤溶酶和凝血酶介导的。对凝血酶和纤溶酶可能作用模式的研究表明，这些酶能够作用于细胞本身以及细胞产生的物质。对细胞的影响表现为有丝分裂活动，有时也表现为细胞损伤和死亡。尽管这些影响影响了尿激酶的水平，但酶对细胞产生的物质的作用最好地解释了产量的提高。对纤溶酶和凝血酶以及胰酶的研究表明，蛋白水解酶可以通过各种方式发挥作用--影响尿激酶的稳定性，干扰天然抑制剂(S)对尿激酶的抑制，以及从非活性物质中诱导尿激酶活性。血浆和凝血酶似乎主要通过后一种机制起作用。在肾、肺、脾和甲状腺的培养中发现了非活性物质，这些物质在接触蛋白水解酶时产生尿激酶，可能代表尿激酶前体。处于这种非活性状态的尿激酶似乎很容易被酶，特别是纤溶酶和凝血酶激活，从而促进纤维蛋白的去除，并可能也提供了过度纤溶的途径。
Lysis of fibrin in tissue culture has been shown to be due to plasminogen activator identified immunologically as urokinase. The present study examines fibrinolytic events in culture, particularly mechanisms leading to increased urokinase levels and accelerated fibrinolysis. Deposition of fibrin on cells in culture was followed by a two- to six-fold increase in urokinase in the supernates and rapid disappearance of the fibrin. Investigation of factors that might be responsible for these events (including fibrin, fibrinogen, vasoactive stimuli, and the enzymes thrombin and plasmin) indicated that the enhanced urokinase yields were mediated through plasmin and thrombin. Study of the possible modes of action of thrombin and plasmin indicated that these enzymes are capable of acting on the cells themselves as well as on cell-produced material. The effect on cells was manifested by mitotic activity or, occasionally, cell injury and death. Although these effects influenced urokinase levels, enhanced yields were explained best by the action of enzymes on cellproduced material. Studies with plasmin and thrombin, and also trypsin, indicated that proteolytic enzymes may act in various ways-affect the stability of urokinase, interfere with inhibition of urokinase by naturally occurring inhibitor(s), and induce urokinase activity from inactive material. Plasma and thrombin appeared to act primarily through the latter mechanism. Inactive material, which gave rise to urokinase upon exposure to proteolytic enzymes and which may represent urokinase precursor, was found in cultures of kidney, lung, spleen, and thyroid. Urokinase in such inactive state appears to be readily accessible to activation by enzymes, particularly plasmin and thrombin, thus facilitating removal of fibrin and possibly also providing pathways to excessive fibrinolysis.