Roles of mast cells and PMN leukocytes in cardiotoxin-induced rat paw edema

Abstract

Cardiotoxin, isolated from the venom of Naja naja atra, was found to cause rat hind-paw edema in a dose-dependent manner. This edematous response was significantly suppressed by pretreatment with diphenhydramine, methysergide or compound 48/80, which reduced the tissue histamine content. Polymorphonuclear (PMN) leukocyte infiltration appeared within 1 h and had accumulated markedly in the rat paw 3–6 h after subplantar injection of cardiotoxin. Methotrexate pretreatment significantly reduced not only the peripheral leukocyte count but also cardiotoxin-induced paw edema. Captopril, a kininase inhibitor, potentiated the edematous response caused by a low dose of cardiotoxin. The initial phase, occuring within 3 h, of paw edema induced by cardiotoxin was suppressed by trasylol, [Thi 5, 8, D-Phe 7] bradykinin, or by cellulose sulfate pretreatment which greatly reduced plasma kininogen levels. Both mast cells and PMN leukocytes possess kinin-forming activities, but with different properties. The kinin-forming activity of mast cells but not of PMN leukocytes was inhibited by trasylol. In isolated mast cells, cardiotoxin caused a dose-dependent release of histamine, β-glucuronidase, lactate dehydrogenase and kinin-forming activity. These observations suggest that mast cells and PMN leukocytes are involved in cardiotoxin-induced paw edema, and that inflammatory mediators such as histamine, serotonin and kinins were supplied directly or indirectly by mast cells, at least in the initial phase.