Thromb Haemost 1992; 68(06): 657-661
DOI: 10.1055/s-0038-1646339
Original Article
Schattauer GmbH Stuttgart

Vitronectin Modulates Glycosaminoglycan Dependent Reactions of Protein C Inhibitor

Dietmar Seiffert
The Laboratory for Clinical Experimental Physiology, Department of Medical Physiology, University of Vienna, Austria
,
Margarethe Geiger
The Laboratory for Clinical Experimental Physiology, Department of Medical Physiology, University of Vienna, Austria
,
Sonja Ecke
The Laboratory for Clinical Experimental Physiology, Department of Medical Physiology, University of Vienna, Austria
,
Bernd R Binder
The Laboratory for Clinical Experimental Physiology, Department of Medical Physiology, University of Vienna, Austria
› Author Affiliations
Further Information

Publication History

Received 19 May 1992

Accepted after revision 22 July 1992

Publication Date:
04 July 2018 (online)

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Summary

Protein C inhibitor (PCI), a glycosaminoglycan (GAG) dependent serine protease inhibitor, inhibits its target proteases by forming SDS-stable 1:1 complexes. GAGs alter target enzyme specificity of PCI in such a way that e.g. urokinase (uPA) is the preferred target enzyme in the presence of GAGs while in their absence preferentially tissue kallikrein (TK) complexes are formed.

The effect of the GAG-binding adhesive glycoprotein vitronectin (Vn) on the GAG-stimulated inhibition of uPA by PCI was studied using an amidolytic assay. In the presence of heparin, Vn protected uPA from inhibition by PCI in a dose-dependent manner with respect to both, Vn- and heparin-concentration. Vn also was active when heparin was replaced by low-molecular weight heparin or heparan sulfate, respectively. In the absence of GAGs, Vn had no effect on the inhibition of uPA by PCI.

In a similar system, Vn was far less effective in modifying the inhibitory function of heparin on the inhibition of TK by PCI. When equimolar concentrations of radiolabelled uPA and TK were incubated with PCI in the presence of heparin, only complexes of PCI with uPA were detectable. Addition of Vn reduced this complex formation, whereas, in contrast, complexes of PCI and TK appeared. These results indicate that Vn modulates both, the activity and specificity of PCI and suggest different structural heparin-requirements for the PCI/uPA versus PCI/TK interaction.