LIPOXYGENASE-DERIVED MEDIATORS MAY BE INVOLVED IN IN-VIVO NEUTROPHIL MIGRATION INDUCED BY BOTHROPS ERYTHROMELAS AND BOTHROPS ALTERNATUS VENOMS

Bothrops erythromelas (BEV) and B. alternatus (BAV) venoms induced a d ose-dependent neutrophil migration when injected into rat peritoneal c avities (20-160 mu g/cavity). These venoms (80 mu g/rat) also induced neutrophil migration in the air pouch model of inflammation. This migr atory response seemed to be related to the phospholipase A(2) (PLA(2)) activity of the venoms. BAV had approximately two times more PLA(2) a ctivity than BEV, and the neutrophil migration induced by the former v enom was two to three-fold greater than that observed with the latter. Heated (90 degrees C for 5 min) BEV lost about 50% of its PLA(2) acti vity and this was accompanied by a corresponding loss in the ability t o induce neutrophil chemotaxis. Dexamethasone (0.5 mg/kg, s.c.), an in direct inhibitor of PLA(2) activity, also abolished the neutrophil mig ration induced by both venoms. Since NDGA (100 mg/kg, s.c.) and dexame thasone, but not indomethacin (2 mg/kg, s.c.), strongly reduced the ne utrophil migration induced by both bothropic venoms, it is suggested t hat arachidonate-derived lipoxygenase metabolites such as leukotriene B-4 act as the chemotactic mediators. Macrophages could be the main ce llular source of such metabolites since they are the predominant resid ent cells in the rat air pouch, and the migratory response of BEV and BAV into peritoneal cavities was potentiated in rats pretreated with t hioglycollate. The neutrophil migration induced by BEV and BAV was not due to endotoxin contamination since heated BEV showed no effect and polymyxin B-treated BAV still remained active.