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Thromb Haemost 1993; 70(05): 867-872
DOI: 10.1055/s-0038-1649685
Fibrinolysis
Schattauer GmbH Stuttgart

Interaction of Plasminogen Activators and Plasminogen with Heparin: Effect of Ionic Strength

Dingeman C Rijken
The TNO Institute of Ageing and Vascular Research (IVVO-TNO), Gaubius Laboratory, Leiden, The Netherlands
,
Gerard A W de Munk
The TNO Institute of Ageing and Vascular Research (IVVO-TNO), Gaubius Laboratory, Leiden, The Netherlands
,
Annie F H Jie
The TNO Institute of Ageing and Vascular Research (IVVO-TNO), Gaubius Laboratory, Leiden, The Netherlands
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Publication History

Received 25 March 1993

Accepted after revision 21 June 1993

Publication Date:
05 July 2018 (online)

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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.