ASSEMBLY AND ACTIVATION OF THE INTRINSIC FIBRINOLYTIC PATHWAY ON THE SURFACE OF HUMAN ENDOTHELIAL-CELLS IN CULTURE

Factor XII has long been implicated in the intrinsic pathway of fibrin olysis, but the mechanism by which it triggers plasminogen activation and targets fibrinolysis has not been established. in the present stud y, the assembly and function of activated Factor XII (F.XIIa), prourok inase (pro-u-PA), high molecular weight kininogen (H-kininogen), and p rekallikrein on human umbilical vein endothelial cells (HUVEC) was inv estigated. I-125-prekallikrein was shown to bind to HUVEC via receptor -bound H-kininogen in the presence of 50 mu M ZnCl2. After the additio n of F.XIIa, 78% of the I-125-prekallikrein initially bound to HUVEC w as converted to I-125-kallikrein, However, only 6% of the HUVEC-bound I-125-pro-u-PA was thereby activated. This discrepancy was shown to be related to rapid dissociation (>50% within 15 min) of prekallikrein/k allikrein, but not pro-u-PA, from HUVEC. Increasing the level of cell- bound kallikrein increased the portion of cell-bound pro-u-PA activate d, indicating that their co-localization was important for this pathwa y. Finally, F.XIIa was shown to trigger plasminogen activation on HUVE C via this pathway. This assembly of reactants on the endothelium sugg ests a mechanism whereby local fibrinolysis may be triggered by blood coagulation.