Summary
Increasing concentrations of EACA produce a biphasic pattern of inhibition and enhancement
of urokinase-induced lysis of bovine fibrin containing bovine plasminogen, while the
inhibition of fibrinolysis induced by a porcine tissue plasminogen activator increases
uniformly. The biphasic EACA pattern is also observed with human plasminogen in fibrinolytic
and caseinolytic assays of urokinase. The biphasic EACA pattern produced with urokinase
is related to the presence of a genuine form of plasminogen. The enhancement phase
is caused by an increased rate of plasminogen activation in the presence of EACA.
A brief treatment of genuine plasminogen with acid at ionic strength 0.15 results
in an enhanced susceptibility to plasminogen activators and in a partial abolishment
of the biphasic response. These acid-induced alterations of plasminogen seem to be
reversed by acid dialysis at low ionic strength. Other preparations of plasminogen
with enhanced susceptibility to activators have lost the ability to produce a biphasic
pattern of inhibition and enhancement of urokinase-induced plasminogen activation
in the presence of EACA and this ability does not return after acid dialysis at low
ionic strength. EACA inhibits all plasmin preparations, whether prepared from genuine
or altered forms of plasminogen, in the same uniform manner.
Our results show that different forms of plasminogen can be identified by differences
in the susceptibilities to activators, by their response to EACA, and by the reversibility
or irreversibility of the alterations.
