Factor XIIa activation of plasminogen is enhanced by contact activating surfaces and Zn2+.

The native form of plasminogen is Glu-plasminogen, which by plasmin cleavage gives Lys-plasminogen. Lys-plasminogen is a considerably better substrate compared with Glu-plasminogen for plasminogenolytic enzymes. The contact activation of the intrinsic pathway of coagulation consisting of factor XII, prekallikrein and high Mr kininogen has been implicated to play a role in the intrinsic fibrinolysis. Here activation of Glu- and Lys-plasminogen by factor XIIa in the absence of prekallikrein/kallikrein and high Mr kininogen was studied in a purified system by the generation of amidolytic activity towards pyroGlu-Phe-Lys-pNA (S-2403), a chromogenic substrate of plasmin. A slow activation rate of both Glu- and Lys-plasminogen by factor XIIa was enhanced approximately 60-fold in the presence of Zn2+ and a negatively charged surface. 6-Aminohexanoic acid further enhanced the activation of Glu-plasminogen but inhibited the activation of Lys-plasminogen. The presence of a specific factor XIIa inhibitor completely prevented the generation of plasmin amidolytic activity indicating that activation was mediated by proteolytical cleavage, although this could not be proven by Western-blotting. Physiological concentration of factor XIIa was as more efficient than soluble u-PA to lyse fibrin as a result of activation of Glu-plasminogen. This did not require the presence of Zn2+ or sulfatide.