Rat hind-paw swelling effect of an edema-producing protein isolated from Trimeresurus mucrosquamatus snake venom.

TMV F-IV, isolated from the venom of Trimeresurus mucrosquamatus (TMV), caused rat hind-paw edema in a dose-dependent manner. The maximum hind-paw swelling was reached at 1.5-2 h after subplantar injection of TMV F-IV. The edematous response caused by TMV F-IV was suppressed by the s.c. pretreatment with diphenhydramine, methysergide, acetylsalicylic acid or dexamethasone, and by the subplantar co-injection with FPL 55712, a SRS-A antagonist, and BN 52021 or L 652731, both PAF antagonists. Polymorphonuclear (PMN) leukocyte infiltration appeared within 1 h and gradually increased in the rat paw 3-6 h after edema induction. Compound 48/80 or methotrexate pretreatment also inhibited paw edema caused by TMV F-IV. In isolated mast cells, TMV F-IV increased the formation of PGE2 and LTB4 and caused a dose-dependent release of histamine and beta-glucuronidase. Since there are no significant differences in paw edema and mast cell degranulation responses between TMV F-IV and its DFP-modified analogue, the esterase activity may not be necessary in these models. These results indicate that mast cells. PMN leukocytes and some inflammatory mediators such as histamine, serotonin, arachidonate metabolites and PAF are involved in TMV F-IV induced paw edema.