Prothrombin activation during carbon tetrachloride-induced acute liver injury in mice

Serine protease thrombin is a central factor for blood coagulation and is an integral part of inflammatory reactions. Prothrombin activation of the liver homogenates during carbon tetrachloride-induced liver injury was investigated. At 72 h after administration of carbon tetrachloride, the prothrombin activation activity reached the maximal value, and then decreased to the basal level at 168 h. The alanine transaminase (ALT) activity, an index of tissue injury, was dramatically elevated at 36 h after treatment, and almost recovered to normal levels at 72 h. Histochemical analysis revealed that the proliferation of hepatocytes and remarkable phagocytosis by macrophages was observed at 72 h, in contrast to severe tissue damage at 36 h. Finally, we showed that prothrombinase activity, composed of factor Xa and factor Va, was involved in the injury-associated prothrombin activation. Taken together, these results strongly suggest that prothrombin activation by the prothrombinase complex occurred following tissue destruction in carbon tetrachloride-induced liver injury.