title: Activation of J77A.1 macrophages by three phospholipases A2 isolated from Bothrops atrox snake venom.
abstract: In the present study, we investigated the in vitro effects of two basic myotoxic phospholipases A2 (PLA2), BaTX-I, a catalytically inactive Lys-49 variant, and BaTX-II, a catalytically active Asp-49, and of one acidic myotoxic PLA2, BaPLA2, a catalytically active Asp-49, isolated from Bothrops atrox snake venom, on the activation of J774A.1 macrophages. At noncytotoxic concentrations, the toxins did not affect the adhesion of the macrophages, nor their ability to detach. The data obtained showed that only BaTX-I stimulated complement receptor-mediated phagocytosis. However, BaTX-I, BaTX-II, and BaPLA2 induced the release of the superoxide anion by J774A.1 macrophages. Additionally, only BaTX-I raised the lysosomal volume of macrophages after 15 min of incubation. After 30 min, all the phospholipases increased this parameter, which was not observed within 60 min. Moreover, BaTX-I, BaTX-II, and BaPLA2 increased the number of lipid bodies on macrophages submitted to phagocytosis and not submitted to phagocytosis. However, BaTX-II and BaPLA2 induced the release of TNF-α by J774A.1 macrophages. Taken together, the data show that, despite differences in enzymatic activity, the three toxins induced inflammatory events and whether the enzyme is acidic or basic does not seem to contribute to these effects.
authors.affiliation: Laboratório de Imunofarmacologia Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ-Rondônia, Rua da Beira, 7671 Br364, Km 3.5, 76812-245 Porto Velho, RO, Brazil.
authors.forename: Juliana L
authors.initials: JL
authors.lastname: Furtado
authors.affiliation: Centro de Biomoléculas Aplicadas à Saúde, FIOCRUZ-Rondônia e Departamento de Medicina, Universidade Federal de Rondônia (UNIR), Campus BR 364, Km 9.5, 76801-059 Porto Velho, RO, Brazil.
authors.forename: George A
authors.initials: GA
authors.lastname: Oliveira
authors.affiliation: Laboratório de Imunofarmacologia Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ-Rondônia, Rua da Beira, 7671 Br364, Km 3.5, 76812-245 Porto Velho, RO, Brazil.
authors.forename: Adriana S
authors.initials: AS
authors.lastname: Pontes
authors.affiliation: Laboratório de Imunofarmacologia Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ-Rondônia, Rua da Beira, 7671 Br364, Km 3.5, 76812-245 Porto Velho, RO, Brazil.
authors.forename: Sulamita da S
authors.initials: Sda S
authors.lastname: Setúbal
authors.affiliation: Laboratório de Imunofarmacologia Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ-Rondônia, Rua da Beira, 7671 Br364, Km 3.5, 76812-245 Porto Velho, RO, Brazil.
authors.forename: Caroline V
authors.initials: CV
authors.lastname: Xavier
authors.affiliation: Laboratório de Imunofarmacologia Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ-Rondônia, Rua da Beira, 7671 Br364, Km 3.5, 76812-245 Porto Velho, RO, Brazil.
authors.forename: Fabianne
authors.initials: F
authors.lastname: Lacouth-Silva
authors.affiliation: Laboratório de Imunofarmacologia Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ-Rondônia, Rua da Beira, 7671 Br364, Km 3.5, 76812-245 Porto Velho, RO, Brazil.
authors.forename: Beatriz F
authors.initials: BF
authors.lastname: Lima
authors.affiliation: Centro de Biomoléculas Aplicadas à Saúde, FIOCRUZ-Rondônia e Departamento de Medicina, Universidade Federal de Rondônia (UNIR), Campus BR 364, Km 9.5, 76801-059 Porto Velho, RO, Brazil.
authors.forename: Kayena D
authors.initials: KD
authors.lastname: Zaqueo
authors.affiliation: Centro de Biomoléculas Aplicadas à Saúde, FIOCRUZ-Rondônia e Departamento de Medicina, Universidade Federal de Rondônia (UNIR), Campus BR 364, Km 9.5, 76801-059 Porto Velho, RO, Brazil.
authors.forename: Anderson M
authors.initials: AM
authors.lastname: Kayano
authors.affiliation: Centro de Biomoléculas Aplicadas à Saúde, FIOCRUZ-Rondônia e Departamento de Medicina, Universidade Federal de Rondônia (UNIR), Campus BR 364, Km 9.5, 76801-059 Porto Velho, RO, Brazil.
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Calderon
authors.affiliation: Laboratório de Imunofarmacologia Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ-Rondônia, Rua da Beira, 7671 Br364, Km 3.5, 76812-245 Porto Velho, RO, Brazil ; Centro de Biomoléculas Aplicadas à Saúde, FIOCRUZ-Rondônia e Departamento de Medicina, Universidade Federal de Rondônia (UNIR), Campus BR 364, Km 9.5, 76801-059 Porto Velho, RO, Brazil.
authors.forename: Rodrigo G
authors.initials: RG
authors.lastname: Stábeli
authors.affiliation: Centro de Biomoléculas Aplicadas à Saúde, FIOCRUZ-Rondônia e Departamento de Medicina, Universidade Federal de Rondônia (UNIR), Campus BR 364, Km 9.5, 76801-059 Porto Velho, RO, Brazil.
authors.forename: Andreimar M
authors.initials: AM
authors.lastname: Soares
authors.affiliation: Laboratório de Imunofarmacologia Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ-Rondônia, Rua da Beira, 7671 Br364, Km 3.5, 76812-245 Porto Velho, RO, Brazil ; Centro de Biomoléculas Aplicadas à Saúde, FIOCRUZ-Rondônia e Departamento de Medicina, Universidade Federal de Rondônia (UNIR), Campus BR 364, Km 9.5, 76801-059 Porto Velho, RO, Brazil.
authors.forename: Juliana P
authors.initials: JP
authors.lastname: Zuliani
mesh_terms: D000818:Animals; D017837:Bothrops; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D010587:Phagocytosis / Q000187:drug effects; D054467:Phospholipases A2 / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D012910:Snake Venoms / Q000201:enzymology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D012910:Snake Venoms; D014409:Tumor Necrosis Factor-alpha; D054467:Phospholipases A2