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.
Wang
J P
JP
Department of Medical Research, Taichung Veterans General Hospital, Taipei, Taiwan.
Teng
C M
CM
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