Rat protein SV-IV (seminal vesicle protein No. 4) accelerates human blood coagulation in vitro by selective inhibition of antithrombin III

Abstract

The seminal vesicle protein No. 4 (SV-IV) secreted from the rat seminal vesicle epithelium, possesses immunosuppressive and anti-inflammatory properties and it is a potent inhibitor of platelet aggregation both in vivo and in vitro. This research aimed to investigate the possible effect of SV-IV on the process of human blood coagulation. Preliminary experiments showed that the recalcification time (RT) of platelet-poor plasma (PPP) samples, obtained from both normal subjects and patients affected by some hemorrhagic disorders, was found to be markedly reduced in the presence of micromolar amounts of SV-IV. It was demonstrated that the concentration of free antithrombin III (AT III) occurring in blood sera obtained from PPP samples recalcified in the presence of SV-IV was significantly decreased in comparison with sera obtained from PPP recalcified in the absence of SV-IV. It was also shown that PPP treatment with SV-IV significantly reduced the concentration of free AT III without affecting the levels of other plasma serine protease inhibitors, such as α 2-macroglobulin, α 1-antitrypsin and C 1-inhibitor. In addition, the RT of PPP treated with a specific rabbit anti-AT III polyclonal antiserum (anti-AT III treated PPP) was not modified by SV-IV. These findings were confirmed by the observation that the addition of SV-IV into an in vitro coagulation system, containing pure fibrinogen, α-thrombin and AT-III, resulted in complete suppression of thrombin inhibition by AT III. No other steps of the blood clotting process (prothrombinase complex, factor XIII, fibrinogen concentration) were affected by SV-IV.