Activation of a plasma fraction containing unactivated
Hageman factor and
prekallikrein followed by chromatography of this fraction on
DEAE-cellulose revealed four peaks having
bradykinin-generating activity. Peak 1 contained
kallikrein; peaks 2-3, 4, and 5 each contained
prekallikrein-activating activity. Elution of peaks 2-3, 4, and 5 from disc
gels after electrophoresis at pH 9.3 revealed peaks of
prekallikrein-activating activity located at 5-8, 11-12, 15-16, and 20-26 mm, each of which was associated with a peak of clot-promoting activity which specifically corrected
Hageman factor deficiency. Conversion of peak 2 to peaks 3, 4, and 5 was associated with a progressive decrease in size, increase in net negative charge, increased
prekallikrein-activating activity, and decreased ability to correct
Hageman factor deficiency.
Plasminogen and
plasmin were found on a
DEAE-cellulose chromatogram of serum overlapping peaks 2 and 3. Incubation of active
Hageman factor with
streptokinase-activated
plasminogen resulted in enhanced ability of the mixture to activate
prekallikrein. Assessment of the products of this reaction by disc gel electrophoresis demonstrated the formation of the
prealbumin prekallikrein activator corresponding to the major
prekallikrein activator generated by contact activation of human plasma. The conversion of
plasminogen to
plasmin and the subsequent cleavage of
Hageman factor by
plasmin to form activators of
prekallikrein represents one pathway in which coagulation, fibrinolysis, and
inflammation are linked.