Ellis V, Whawell S A
Thrombosis Research Institute, London, UK.
Blood. 1997 Sep 15;90(6):2312-22.
Plasminogen activators play a role in the response of the vessel wall to injury, presumably by mediating the degradation of extracellular matrix (ECM) by vascular smooth muscle cells (VSMCs) that is necessary for their migration and proliferation. We have therefore investigated the ability of VSMCs to assemble specific cell surface plasminogen-activating systems. Urokinase-type plasminogen activator (uPA) bound to a single class of site on VSMCs (kd, 2 nmol/L), binding of pro-uPA resulted in a large potentiation of plasmin generation and both were competed by antibodies to the uPA receptor (uPAR). Tissue-type plasminogen activator (tPA) also bound to VSMCs as determined by functional assay, with the binding isotherms showing two classes of binding site with apparent kds of 25 and 300 nmol/L. tPA binding to the higher affinity site caused a greater than 90-fold enhancement of the activation of cell bound plasminogen, whereas the lower affinity binding, mediated primarily by the ECM, had little effect on tPA activity. The high-affinity binding of tPA to VSMCs resulted in an eightfold greater potential for plasmin generation than the binding of uPA, with this difference increasing to 15-fold after thrombin stimulation of the cells due to a 1.8-fold increase in tPA binding. These data show a novel specific tPA receptor on VSMCs that may be important for the regulation of plasminogen activation in various vascular pathologies.
纤溶酶原激活剂在血管壁对损伤的反应中发挥作用，可能是通过介导血管平滑肌细胞（VSMC）对细胞外基质（ECM）的降解来实现的，而这种降解是VSMC迁移和增殖所必需的。因此，我们研究了VSMC组装特定细胞表面纤溶酶原激活系统的能力。尿激酶型纤溶酶原激活剂（uPA）与VSMC上的一类单一位点结合（解离常数kd为2 nmol/L），pro-uPA的结合导致纤溶酶生成大幅增强，且两者均被抗uPA受体（uPAR）抗体竞争。通过功能测定确定，组织型纤溶酶原激活剂（tPA）也与VSMC结合，结合等温线显示有两类结合位点，表观解离常数分别为25和300 nmol/L。tPA与高亲和力位点的结合使细胞结合的纤溶酶原激活增强了90倍以上，而主要由ECM介导的低亲和力结合对tPA活性影响很小。tPA与VSMC的高亲和力结合导致纤溶酶生成的潜力比uPA的结合大八倍，在凝血酶刺激细胞后，由于tPA结合增加1.8倍这种差异增加到15倍。这些数据表明VSMC上存在一种新的特异性tPA受体，这可能对各种血管病变中纤溶酶原激活的调节很重要。
