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.
