Roles of PMN leucocytes, platelets and some mediators in rat hind-paw oedema induced by two phospholipase A2 enzymes from Trimeresurus mucrosquamatus venom.
Two phospholipase A2 (PLA2) enzymes, TMVPLA2 I and TMVPLA2 II, isolated from Trimeresurus mucrosquamatus venom induced rat hind-paw oedema. Recovered myeloperoxidase activity increased within 1 h and was greatly elevated in the rat paw 3-6 h after subplantar injection of these venom PLA2 enzymes. Methotrexate pretreatment significantly reduced not only the peripheral leucocyte count but also venom PLA2-induced paw oedema. In rat isolated PMN leucocyte suspension, venom PLA2 induced superoxide radical formation. Paw swelling caused by TMVPLA2 I or TMVPLA2 II was only slightly or not, respectively, reduced in the rats pretreated with anti-platelet plasma, which reduced peripheral blood platelet count by greater than 96%, suggesting platelets are not involved. In isolated platelet preparation, TMVPLA2 I induced platelet activation in a concentration-dependent manner, while TMVPLA2 II had no effect. Pretreatment with diphenhydramine/methysergide greatly suppressed the oedematous responses caused by the two venom PLA2 enzymes; the residual responses were significantly further depressed by aspirin. The oedematous responses caused by the enzymes were also suppressed by FPL 55712, BW 755C, dexamethasone, superoxide dismutase/catalase, isoprenaline and terbutaline. However, BN 52021 and L 652731, both platelet aggregating factor antagonists, were not effective on these responses. Thus, in addition to histamine and 5-hydroxytryptamine release by the mast cells in PLA2-induced paw oedema (Wang & Teng 1990), the results of this study indicate minor, but significant, roles for neutrophils and inflammatory mediators including prostaglandins, leukotrienes and superoxide radicals.
Department of Medical Research, Taichung Veterans General Hospital, Taipei, Taiwan.
J P
JP
Wang
C M
CM
Teng
D000255:Adenosine Triphosphate / Q000097:blood; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016718:Arachidonic Acid / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D003435:Crotalid Venoms / Q000633:toxicity*; D004487:Edema / Q000139:chemically induced* / Q000201:enzymology / Q000503:physiopathology; D066298:In Vitro Techniques; D007705:Kinins / Q000378:metabolism; D008727:Methotrexate / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009195:Peroxidase / Q000302:isolation & purification / Q000378:metabolism; D010741:Phospholipases A / Q000633:toxicity*; D054467:Phospholipases A2; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003435:Crotalid Venoms; D007705:Kinins; C029748:Trimeresurus venoms; D016718:Arachidonic Acid; D000255:Adenosine Triphosphate; D009195:Peroxidase; D010741:Phospholipases A; D054467:Phospholipases A2; D008727:Methotrexate