Trocarin, a blood coagulation factor Xa homologue from snake venom, causes inflammation and mitogenesis

Trocarin, a Group D prothrombin activator from Tropidechis carinatus snake venom, has high sequence similarity to blood coagulation factor Xa (FXa). Both trocarin and FXa activate prothrombin to mature thrombin and have similar requirements for cofactors, such as factor Va, Ca2+ ions and phospholipids. In addition to its hemostatic functions, human FXa causes inflammation and induces mitogenesis in several cell types due to its interaction with effector protease receptor-1 (EPR-1). The inter-EGF domain region (L83FTKRL88) of FXa implicated in EPR-1-binding is distinctly different in trocarin (K83VLYQS88). Here we show that, interestingly, trocarin also causes edema in the mouse footpad; the inflammation, accompanied by a large purplish clot, is more persistent than the transient edema caused by FXa. Histological examination indicates significant differences between edema induced by FXa and trocarin. Moreover, trocarin-induced edema is not inhibited by a synthetic peptide based on the FXa-binding region of EPR-1, indicating that the inflammation is probably mediated by a mechanism independent of EPR-1-binding. Trocarin, like FXa, also has a mitogenic effect on bronchial smooth muscle cells mediated by an EPR-1-independent mechanism. Hence trocarin, being closely related to FXa, has similar non-hemostatic functions in mediating inflammation and mitogenesis, yet appears to act by distinctly different mechanisms.