Fibrinolytic properties of activated FXII.
Activated factor XII (FXIIa), the initiator of the contact activation system, has been shown to activate plasminogen in a purified system. However, the quantitative role of FXIIa as a plasminogen activator in contact activation-dependent fibrinolysis in plasma is still unclear. In this study, the plasminogen 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 low PA activity in a purified system. Dextran sulfate potentiated the PA activity of FXIIa about sixfold, but had no effect on the PA activity of smaller fragments of FXIIa, missing the binding domain for negatively charged surfaces. The addition of small amounts of factor XII (FXII) to FXII-deficient plasma induced a large increase in contact activation-dependent PA activity, as measured in a dextran sulfate euglobulin fraction, which may be ascribed to FXII-dependent activation of plasminogen activators like prekallikrein. When more FXII was added, PA activity continued to increase but to a lesser extent. In normal plasma, the addition of FXII also resulted in an increase of contact activation-dependent PA activity. These findings suggested a significant contribution of FXIIa as a direct plasminogen activator. Indeed, at least 20% of contact activation-dependent PA activity could be extracted from a dextran sulfate euglobulin fraction prepared from normal plasma by immunodepletion of FXIIa and therefore be ascribed to direct PA activity of FXIIa. PA activity of endogenous FXIIa immunoadsorped from plasma could 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.
Braat
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Gaubius Laboratory, TNO-PG, Leiden, The Netherlands.
Dooijewaard
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Rijken
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D015153:Blotting, Western; D016264:Dextran Sulfate / Q000494:pharmacology; D005174:Factor XII / Q000378:metabolism*; D015956:Factor XIIa / Q000378:metabolism*; D005342:Fibrinolysis; D006801:Humans; D007700:Kinetics; D010960:Plasminogen Activators / Q000378:metabolism*; D012712:Serum Globulins / Q000302:isolation & purification / Q000378:metabolism
D012712:Serum Globulins; D005174:Factor XII; D016264:Dextran Sulfate; D010960:Plasminogen Activators; D015956:Factor XIIa