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 dose-dependent neutrophil migration when injected into rat peritoneal cavities (20-160 micrograms/cavity). These venoms (80 micrograms/rat) also induced neutrophil migration in the air pouch model of inflammation. This migratory response seemed to be related to the phospholipase A2 (PLA2) activity of the venoms. BAV had approximately two times more PLA2 activity than BEV, and the neutrophil migration induced by the former venom 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 PLA2 activity and this was accompanied by a corresponding loss in the ability to induce neutrophil chemotaxis. Dexamethasone (0.5 mg/kg, s.c.), an indirect inhibitor of PLA2 activity, also abolished the neutrophil migration induced by both venoms. Since NDGA (100 mg/kg, s.c.) and dexamethasone, but not indomethacin (2 mg/kg, s.c.), strongly reduced the neutrophil migration induced by both bothropic venoms, it is suggested that arachidonate-derived lipoxygenase metabolites such as leukotriene B4 act as the chemotactic mediators. Macrophages could be the main cellular source of such metabolites since they are the predominant resident cells in the rat air pouch, and the migratory response of BEV and BAV into peritoneal cavities was potentiated in rats pretreated with thioglycollate. 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.
Flores
C A
CA
Department of Pharmacology, Faculty of Medical Sciences, UNICAMP, Campinas-SP, Brazil.
Zappellini
A
A
Prado-Franceschi
J
J
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D017837:Bothrops; D002630:Chemotactic Factors / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003435:Crotalid Venoms / Q000201:enzymology / Q000633:toxicity*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008084:Lipoxygenase / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010741:Phospholipases A / Q000032:analysis; D054467:Phospholipases A2; D051381:Rats; D017208:Rats, Wistar; D013864:Thioglycolates / Q000494:pharmacology
D001095:Arachidonic Acids; D002630:Chemotactic Factors; D003435:Crotalid Venoms; D013864:Thioglycolates; D009637:Masoprocol; D003907:Dexamethasone; D008084:Lipoxygenase; D010741:Phospholipases A; D054467:Phospholipases A2; D007213:Indomethacin