The Activation of Plasminogen by Hageman Factor and Hageman Factor Fragments

The mechanism of action of Hageman factor (HF, Factor Xll) in surface-mediated conversion of plasminogen to plasmin was investigated, assaying plasmin with H-D-valy 1-L-leucy1-L-1ysi ne p-nitroanalide·2HCL. Unexpectedly, amidolytic activity for this substrate evolved in the presence of kaolin in mixtures of purified preparations of plasminogen and HF, both devoid of detectable prekallikrein and high MW kininogen. The same result was obtained when plasminogen preparations were incubated in the absence of kaolin with HF-fragments prepared by digestion of HF with insoluble trypsin or with gel-filtered HF fragments (approximate MW 30,000). High MW kininogen did not enhance amidolysis in mixtures of plasminogen and HF with kaolin or HF fragments, but both amidolysis and fibrinolysis were enhanced by the fraction of normal plasma not absorbed at low ionic strength to QAE-Sephadex gels at ph 7-5-The analogous fraction of Fletcher trait (prekallikrein deficient) plasma, did not enhance amidolysis or fribrinolysi s. Kinetic study of the HF-kaolin-plasm inogen interaction indicated a direct enzymatic role for the HF moiety acting on plasminogen as a substrate.These data suggest that, contrary to earlier observations, HF or HF-fragments may play a direct role in the activation of plasminogen.