Roles of mast cells and PMN leukocytes in cardiotoxin-induced rat paw edema.
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, occurring within 3 h, of paw edema induced by cardiotoxin was suppressed by trasylol, [Thi5,8,D-Phe7]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, beta-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.
Wang
J P
JP
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
Teng
C M
CM
D000818:Animals; D004179:Cobra Cardiotoxin Proteins / Q000494:pharmacology*; D004487:Edema / Q000139:chemically induced / Q000503:physiopathology*; D004546:Elapid Venoms / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000502:physiology; D066298:In Vitro Techniques; D007704:Kininogens / Q000097:blood; D007705:Kinins / Q000096:biosynthesis; D008297:Male; D008407:Mast Cells / Q000201:enzymology / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology
D004179:Cobra Cardiotoxin Proteins; D004546:Elapid Venoms; D007704:Kininogens; D007705:Kinins; D012701:Serotonin; D006632:Histamine