Summary
In order to define the possible effects of heparin on the fibrinolytic system under
physiological conditions, we studied the interactions of this drug with plasminogen
and its activators at various ionic strengths. As reported in recent literature, heparin
stimulated the activation of Lys-plasminogen by high molecular weight (HMW) and low
molecular weight (LMW) two-chain urokinase-type plasminogen activator (u-PA) and two-chain
tissue-type plasminogen activator (t-PA) 10- to 17-fold. Our results showed, however,
that this stimulation only occurred at low ionic strength and was negligible at a
physiological salt concentration. Direct binding studies were performed using heparin-agarose
column chromatography. The interaction between heparin and Lys-plasminogen appeared
to be salt sensitive, which explains at least in part why heparin did not stimulate
plasminogen activation at 0.15 M NaCl. The binding of u-PA and t-PA to heparinagarose
was less salt sensitive. Results were consistent with heparin binding sites on both
LMW u-PA and the amino-terminal part of HMW u-PA. Single-chain t-PA bound more avidly
than two-chain t-PA. The interactions between heparin and plasminogen activators can
occur under physiological conditions and may modulate the fibrinolytic system.
