Interaction of complement S-protein with thrombin-antithrombin complexes: a role for the S-protein in haemostasis

Complement S-protein is known to function as an inhibitor of the terminal complement sequence (Bhakdi, S. and Tranum-Jensen, J., Biochim. Biophys. Acta 737, 343, 1983). We here report that the S-protein may also play a functional role in haemostasis. Electro-immunoassays performed with the use of poly- and monoclonal antibodies to the protein revealed that it binds to thrombin-anti-thrombin III (T X AT-III) to form stable S X T X AT-III complexes. These complexes form naturally during blood coagulation. They have been identified in human serum and have also been generated in vitro with the respective purified proteins. Formation of the complexes is paralleled by a net protection of thrombin towards the inactivating effects of AT-III, demonstrable in functional assays using a synthetic polypeptide or fibrinogen as substrates for the protease. S-protein may thus exert a promoting effect on blood coagulation and could emerge as a novel component of the blood coagulation system in the future.