Fibrinolytic properties of activated FXII

Activated factor XII (FXIIa), the initiator of the contact activation syste m, has been shown to activate plasminogen in a purified system. However, th e quantitative role of FXIIa as a plasminogen activator in contact activati on-dependent fibrinolysis in plasma is still unclear. In this study, the pl asminogen activator (PA) activity of FXIIa was examined both in a purified system and in a dextran sulfate euglobulin fraction of plasma by measuring fibrinolysis in a fibrin microtiter plate assay. FXIIa was found to have lo w PA activity in a purified system. Dextran sulfate potentiated the PA acti vity of FXIIa about sixfold, but had no effect on the PA activity of smalle r fragments of FXIIa, missing the binding domain for negatively charged sur faces. The addition of small amounts of factor XII (FXII) to FXII-deficient plasma induced a large increase in contact activation-dependent PA activit y, as measured in a dextran sulfate euglobulin fraction, which may be ascri bed to FXII-dependent activation of plasminogen activators like prekallikre in. When more FXII was added, PA activity continued to increase but to a le sser extent. In normal plasma, the addition of FXII also resulted in an inc rease of contact activation-dependent PA activity. These findings suggested a significant contribution of FXIIa as a direct plasminogen activator. Ind eed, at least 20% of contact activation-dependent PA activity could be extr acted from a dextran sulfate euglobulin fraction prepared from normal plasm a by immunodepletion of FXIIa and therefore be ascribed to direct PA activi ty of FXIIa. PA activity of endogenous FXIIa immunoadsorped from plasma cou ld only be detected in the presence of dextran sulfate. From these results it is concluded that FXIIa can contribute significantly to fibrinolysis as a plasminogen activator in the presence of a potentiating surface.