title: A phospholipase A₂ from Bothrops asper snake venom activates neutrophils in culture: expression of cyclooxygenase-2 and PGE₂ biosynthesis.
abstract: In this study, the production of prostaglandin E₂ (PGE₂) and up-regulation in cyclooxygenase (COX) pathway induced by a phospholipase A₂ (PLA₂), myotoxin-III (MT-III), purified from Bothrops asper snake venom, in isolated neutrophils were investigated. The arachidonic acid (AA) production and the participation of intracellular PLA₂s (cytosolic PLA₂ and Ca(2+)-independent PLA₂) in these events were also evaluated. MT-III induced COX-2, but not COX-1 gene and protein expression in neutrophils and increased PGE₂ levels. Pretreatment of neutrophils with COX-2 and COX-1 inhibitors reduced PGE₂ production induced by MT-III. Arachidonyl trifluoromethyl ketone (AACOCF₃), an intracellular PLA₂ inhibitor, but not bromoenol lactone (BEL), an iPLA₂ inhibitor, suppressed the MT-III-induced AA and PGE₂ release. In conclusion, MT-III directly stimulates neutrophils inducing COX-2 mRNA and protein expression followed by production of PGE₂. COX-2 isoform is preeminent over COX-1 for production of PGE₂ stimulated by MT-III. PGE₂ and AA release by MT-III probably is related to cPLA₂ activation.
authors.affiliation: Laboratório de Farmacologia, Instituto Butantan, Av. Vital Brazil 1500, CEP 05503-900, Sao Paulo, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Moreira
authors.forename: José María
authors.initials: JM
authors.lastname: Gutiérrez
authors.forename: Rafaela Bacci
authors.initials: RB
authors.lastname: Amaral
authors.forename: Bruno
authors.initials: B
authors.lastname: Lomonte
authors.forename: Eduardo
authors.initials: E
authors.lastname: Purgatto
authors.forename: Catarina
authors.initials: C
authors.lastname: Teixeira
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D017837:Bothrops; D003435:Crotalid Venoms / Q000737:chemistry*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D054501:Group II Phospholipases A2 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects*; D054467:Phospholipases A2 / Q000494:pharmacology*; D030162:Reptilian Proteins / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D003435:Crotalid Venoms; D016861:Cyclooxygenase Inhibitors; D030162:Reptilian Proteins; D016718:Arachidonic Acid; D051546:Cyclooxygenase 2; D054501:Group II Phospholipases A2; D054467:Phospholipases A2; C080300:myotoxin III, Bothrops asper; D015232:Dinoprostone