CYTOKINE REGULATION OF THE SYNTHESIS OF PLASMINOGEN-ACTIVATOR INHIBITOR-2 BY HUMAN VASCULAR ENDOTHELIAL-CELLS - COMPARISON WITH PLASMINOGEN-ACTIVATOR INHIBITOR-1 SYNTHESIS

Plasminogen activators are inhibited by plasminogen activator inhibitors-1 (PAI-1) and -2 (PAI-2). We describe the synthesis of PAI-2 by human vascular endothelial cells (EC) cultured from umbilical vein, saphenous vein and foreskin microvasculature in response to interleukin-2alpha (IL-1alpha) and tumour necrosis factor alpha (TNFalpha) and compare it with that of PAI-1. Both PAI-2 and PAI-1 were quantitated by ELISAs. PAI-2 was cell-associated while PAI-1 was secreted by EC. IL-1alpha and TNFalpha increased the synthesis of PAI-2 and PAI-1 by EC in a dose-dependent manner. IL-1alpha was a stronger stimulus for PAI-2 synthesis than TNFalpha, while both cytokines were equally effective for PAI-1. Northern blot analysis revealed similar changes in mRNA levels to those in antigen levels. PAI-2 synthesis by cytokine-stimulated EC may be important in thrombus formation and inflammation.