Hyperproduction of fibrin and inefficacy of antithrombin III and alpha2 macroglobulin in the presence of bacterial porins

Abstract

Bacterial porins enhance the thrombin activity upon chromogen substrate chromozym. Should porin-dependent enhancement of thrombin activity take place also upon fibrinogen in vivo, this might greatly increase the fibrin production which, in turn, might lead to blood vessel obstruction. In this study, we demonstrate fibrin hyperproduction in a simplified coagulative system, consisting of fibrinogen and thrombin-pure molecules, in the presence of bacterial porins. In particular, bacterial porins, in the presence of thrombin, significantly increased the fibrin production compared with thrombin alone. Also, fibrin hyperproduction took place even in the presence of the thrombin inhibitors antithrombin III (AT III) or alpha2 macroglobulin (alpha2M). However, the thrombin-fibrinogen reaction in the presence of AT III or alpha2M did not generate fibrin, unless porins were present. In conclusion, porins not only enhance thrombin activity but also inhibit the antithrombin activity exerted by AT III or alpha2M. We hypothesize that, because of porins activity, fibrin is largely generated due to thrombin hyperactivation. Moreover, further fibrin is produced by thrombin, which is not blocked by two serpins for the presence of porins. These results might be relevant as to the occurrence of disseminated intravascular coagulation in sepsis by gram-negative bacteria, which are known to produce porins.