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.