ENDOTHELIAL CELL-MEDIATED CONVERSION OF GLU-PLASMINOGEN TO LYS-PLASMINOGEN - FURTHER EVIDENCE FOR ASSEMBLY OF THE FIBRINOLYTIC SYSTEM ON THE ENDOTHELIAL-CELL SURFACE

Lysing-plasminogen (Lys-PLG), the plasmin-modified form of native glutamic acid-plasminogen (Glu-PLG), displays enhanced binding affinity for fibrin and also enhanced activation by urokinase and tissue plasminogen activator. We previously demonstrated high-affinity, specific, and functional binding of Glu-PLG as well as tissue plasminogen activator to cultured human umbilical vein endothelial cells (HUVEC). In the present study, we demonstrate binding of Lys-PLG to HUVEC, as well as conversion of Glu-PLG to Lys-PLG at the cell surface. Binding of Lys-PLG to HUVEC was saturable, reversible, .epsilon.-aminocaproic acid-sensitive, and involved two saturable sites with Kd''s of 142 pM and 120 nM, respectively. Upon incubation with Glu-PLG, HUVEC, as well as endothelium in situ, partially converted the ligated to a Lys-PLG-like species. Conversion by HUVEC was blocked by diisopropylfluorophosphate, but not by not by other serine protease inhibitors, including .alpha.2-plasmin imhibitor. Eluates of intact umbilical cord vessels contained Lys-PLG by immunoblot analysis. Lys-PLG was also identified immunohistochemically on the endothelial surface of vessels from a variety of normal and inflamed tissues. Thus, endothelial cells appear to actively modify circulating Glu-PLG, bind Lys-PLG to their surface, and thus enhance the fibrinolytic potential of the blood vessel wall.