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Prepublished online as a Blood First Edition Paper on August 7, 2003; DOI 10.1182/blood-2003-05-1551.
Submitted May 22, 2003
Accepted July 13, 2003
Coagulation, inflammation, and apoptosis: different roles for protein S and the protein S-C4b binding protein complex
Suely Meireles Rezende*, Rachel Elizabeth Simmonds, and David Anthony Lane
Department of Haematology, Imperial College of Science, Technology and Medicine, London, United Kingdom; Research Laboratory, HEMOMINAS Foundation, Belo Horizonte, Minas Gerais, Brazil
Department of Biochemistry, University of Hong Kong, Hong Kong, China
* Corresponding author; email: s.rezende{at}ic.ac.uk.
Protein S (PS) has an established role as an important cofactor to activated protein C (APC) in the degradation of coagulation cofactors Va and VIIIa. This anticoagulant role is evident from the consequences of its deficiency, when there is an increased risk of venous thromboembolism (VT). In human plasma, PS circulates ~40% as free PS (FPS) and ~60% in complex with C4b-binding protein (C4BP). Formation of this complex results in loss of PS cofactor function and C4BP can therefore modulate the anticoagulant activity of APC. It had long been predicted that the complex could act as a bridge between coagulation and inflammation due to the involvement of C4BP in regulating complement activation. This prediction was recently supported by the demonstration of binding of the PS-C4BP complex to apoptotic cells. This review aims to summarise recent findings on the structure and functions of PS, the basis and importance of its deficiency, its interaction with C4BP and the possible physiological and pathological importance of the PS-C4BP interaction.
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