Dosne A M, Dubor F, Samama M
Lab. Immunopharmacologie exp., UPR 405 CNRS, Paris, France.
Thromb Res. 1991 Sep 1;63(5):531-9. doi: 10.1016/0049-3848(91)90178-y.
We have studied the effects of PAI-1 on the conversion of scu-PA into tcu-PA in vitro in plasma containing or not a 125I-fibrin clot by determining tcu-PA activity on S2444. Two preparations of PAI-1 have been used, a fraction of medium conditioned with the monkey Vero cells (Vero-Prep), the antiurokinase activity of which is inhibited at 83% by anti PAI-1 IgG, or purified human PAI-1 from HT 1080 fibrosarcoma cells. Scu-PA purified from human kidney cells has been treated with diisopropylfluorophosphate before use. In plasma, conversion of scu-PA into the tc form is accelerated by addition of anti PAI-1 IgG. In plasma containing a clot, generation of tcu-PA, is considerably delayed after addition of the Vero-Prep or human PAI-1. Clot lysis is also decreased but to a lesser extent than it would be expected from the level of tcu-PA activity. Addition of anti PAI-1 antibodies shortens the lag phase before tcu-PA appears and moderatly accelerates clot lysis. These results demonstrate the importance of PAI-1 for the stability of scu-PA in plasma in vitro by delaying its conversion into tcu-PA.
我们通过测定S2444上的tcu-PA活性,研究了纤溶酶原激活物抑制剂-1(PAI-1)在含有或不含有125I-纤维蛋白凝块的血浆中对单链尿激酶型纤溶酶原激活剂(scu-PA)转化为双链尿激酶型纤溶酶原激活剂(tcu-PA)的体外影响。使用了两种PAI-1制剂,一种是用猴Vero细胞培养的培养基上清(Vero-Prep),其抗尿激酶活性被抗PAI-1 IgG抑制83%,另一种是从HT 1080纤维肉瘤细胞中纯化的人PAI-1。从人肾细胞中纯化的scu-PA在使用前用二异丙基氟磷酸处理。在血浆中,添加抗PAI-1 IgG可加速scu-PA向tc形式的转化。在含有凝块的血浆中,添加Vero-Prep或人PAI-1后,tcu-PA的生成显著延迟。凝块溶解也减少,但程度小于根据tcu-PA活性水平预期的程度。添加抗PAI-1抗体可缩短tcu-PA出现前的延迟期,并适度加速凝块溶解。这些结果表明,PAI-1通过延迟scu-PA转化为tcu-PA,对体外血浆中scu-PA的稳定性具有重要作用。