Synergistic Cofactor Function of Factor V and Protein S to Activated Protein C in the Inactivation of the Factor Villa – Factor IXa Complex

Lei Shea; Xuhua He; Björn Dahlbäck

doi:10.1055/s-0038-1657682

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1997; 78(03): 1030-1036
DOI: 10.1055/s-0038-1657682

Rapid Communication

Schattauer GmbH Stuttgart

Synergistic Cofactor Function of Factor V and Protein S to Activated Protein C in the Inactivation of the Factor Villa – Factor IXa Complex

Species Specific Interactions of Components of the Protein C Anticoagulant System

Authors

Lei Shea

The Department of Clinical Chemistry, Lund University, the Wallenberg Laboratory, University Hospital, Malmö, Malmö, Sweden
Xuhua He

The Department of Clinical Chemistry, Lund University, the Wallenberg Laboratory, University Hospital, Malmö, Malmö, Sweden
Björn Dahlbäck

The Department of Clinical Chemistry, Lund University, the Wallenberg Laboratory, University Hospital, Malmö, Malmö, Sweden

Abstract

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Summary

Human factor V has been shown not only to be a precursor to procoagulant factor Va but also to express anticoagulant properties. Thus, factor V was recently found to potentiate the effect of protein S as cofactor to activated protein C (APC) in the inactivation of the factor VIIIa-factor IXa complex. The purpose of this study was to determine whether the APC-cofactor function of factor V was also expressed in the bovine protein C system and to elucidate the molecular background for the species specificity of APC. For this purpose, the effects of protein S and factor V on APC-mediated inactivation of factor VIIIa were studied using purified APC, protein S and factor V of human and bovine.origin. The factor VIIIa investigated here was part of a Xase complex (i.e. factor IXa, factor VIIIa, phospholipid and calcium) and the APC-mediated inhibition of factor VIIIa was monitored by the ability of the Xase complex to activate factor X. Synergistic APC-cofactor function of factor V and protein S was demonstrated in the bovine system. The effect of bovine APC was potentiated by bovine protein S but not by human protein S, whereas both human or bovine protein S stimulated the function of human APC. Factor V did not express species specificity in its APC-cofactor activity even though bovine factor V was more potent than its human counterpart. Recombinant human/bovine protein S chimeras were used to demonstrate that the thrombin sensitive region and first epidermal growth factor-like module of protein S determine the species specificity of the APC-protein S interaction. In conclusion, both human and bovine factor V were found to express APC-cofactor activity which depends on the presence of protein S. The species specificity of APC was shown to be caused by the interaction between APC and protein S.

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References

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