VASCULAR SMOOTH-MUSCLE CELLS POTENTIATE PLASMIN GENERATION BY BOTH UROKINASE AND TISSUE-PLASMINOGEN ACTIVATOR-DEPENDENT MECHANISMS - EVIDENCE FOR A SPECIFIC TISSUE-TYPE PLASMINOGEN-ACTIVATOR RECEPTOR ON THESE CELLS

Plasminogen activators play a role in the response of the vessel wall to injury, presumably by mediating the degradation of extracellular ma trix (ECM) by vascular smooth muscle cells (VSMCs) that is necessary f or their migration and proliferation. We have therefore investigated t he ability of VSMCs to assemble specific cell surface plasminogen-acti vating systems. Urokinase-type plasminogen activator (uPA) bound to a single class of site on VSMCs (kd, 2 nmol/L), binding of pro-uPA resul ted in a large potentiation of plasmin generation and both were compet ed by antibodies to the uPA receptor (uPAR). Tissue-type plasminogen a ctivator (tPA) also bound to VSMCs as determined by functional assay, with the binding isotherms showing two classes of binding site with ap parent kds of 25 and 300 nmol/L, tPA binding to the higher affinity si te caused a greater than 90-fold enhancement of the activation of cell bound plasminogen, whereas the lower affinity binding, mediated prima rily 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 incr easing 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 re ceptor on VSMCs that may be important for the regulation of plasminoge n activation in various vascular pathologies. (C) 1997 by The American Society of Hematology.