title: Bothrops lanceolatus (Fer de lance) venom stimulates leukocyte migration into the peritoneal cavity of mice.
abstract: The ability of Bothrops lanceolatus venom to induce neutrophil migration into the peritoneal cavity of mice was investigated. Intraperitoneal injection of venom caused dose- and time-dependent neutrophil migration, which peaked with 750 ng of venom/cavity 4h after venom injection. The neutrophil migration was significantly reduced by pretreatment with dexamethasone (0.5 mg/kg, s.c.), an indirect inhibitor of phospholipase A(2) (PLA(2)), and AA861 (0.01 mg/kg, s.c.), a 5-lipoxygenase inhibitor, but in contrast, was not modified by pretreatment with indomethacin (2 mg/kg, s.c.), an inhibitor of the cyclooxygenase pathway, meloxicam (5 mg/kg, s.c.), an inhibitor of the cyclooxygenase-2 pathway, or the PAF inhibitor WEB2086 (40 mg/kg, s.c.). Dexamethasone and AA861 also inhibited the neutrophil migration by 60% when administered immediately after venom injection, and the coadministration of these two drugs caused a 75% reduction in migration. BLV-induced neutrophil migration was not due to contamination by endotoxin since polymyxin B-treated venom retained its activity. Heating the venom (97 degrees C, 2 min) reduced the PLA(2) activity by 64% and this was accompanied by a corresponding reduction (68%) in neutrophil migration. These results suggest that arachidonate-derived lipoxygenase metabolites (possibly leukotriene B(4)) are involved in the chemotaxis observed. Macrophages may be an important source of these metabolites since the migratory response to venom was potentiated in mice pretreated with thioglycollate, but reduced when the peritoneal cavity was washed with sterile saline.
authors.affiliation: Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), CP 6111, 13083-970, Campinas, SP, Brazil.
authors.forename: Vanessa Alves
authors.initials: VA
authors.lastname: Arruda
authors.forename: Alessandra
authors.initials: A
authors.lastname: de Queiroz Guimarães
authors.forename: Stephen
authors.initials: S
authors.lastname: Hyslop
authors.forename: Paulo Maria Ferreira
authors.initials: PM
authors.lastname: de Araújo
authors.forename: Cassian
authors.initials: C
authors.lastname: Bon
authors.forename: Albetiza Lôbo
authors.initials: AL
authors.lastname: de Araújo
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology; D017837:Bothrops; D002464:Cell Migration Inhibition; D003435:Crotalid Venoms / Q000008:administration & dosage / Q000633:toxicity*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects*; D010741:Phospholipases A / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology
chemical_list: D001381:Azepines; D016227:Benzoquinones; D003435:Crotalid Venoms; D014230:Triazoles; C052518:WEB 2086; D003907:Dexamethasone; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D010741:Phospholipases A; D007213:Indomethacin