Signaling pathways involved in zymosan phagocytosis induced by two secreted phospholipases A(2) isolated from Bothrops asper snake venom in macrophages

Autor(es)

Zuliani, Juliana Pavan ^{[1, 2, 3]} ; Maria Gutierrez, Jose ^[4] ; Teixeira, Catarina ^[2]

Afiliação do(s) autor(es)

^[1] Univ Fed Rondonia, UNIR, Dept Med, Porto Velho, RO - Brazil

^[2] Inst Butantan, Lab Farmacol, Ave Vital Brazil 1500, BR-05503900 Sao Paulo, SP - Brazil

^[3] Fundacao Oswaldo Cruz Rondonia FIOCRUZ RO, Lab Imunol Celular Aplicada Saude, Porto Velho, RO - Brazil

^[4] Univ Costa Rica, Fac Microbiol, Inst Clodomiro Picado, San Jose - Costa Rica

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Biological Macromolecules; v. 113, p. 575-582, JUL 1 2018.
• Citações Web of Science: 2

Resumo

Phagocytosis, a process involved in host defense, requires coordination of a variety of signaling reactions. MT-II, a catalytically-inactive Lys49-PLA(2), and MT-III, an active Asp49-PLA(2) isolated from Bothrops asper snake venom, activate phagocytosis in macrophages. In this study the signal pathways mediating zymosan phagocytosis, focusing in lipidic second messengers, were investigated. Macrophages collected from male Swiss mouse peritoneum were obtained 96 h after i.p. injection of thioglycollate. Phagocytosis was evaluated with non-opsonized zymosan in the presence or absence of specific inhibitors. Data showed that both venom PLA(2)s increased phagocytosis. Zileuton, Etoricoxib, PACOCF3 (5-LO, COX-2 and iPLA(2) inhibitors, respectively), as well as WEB2170 (PAF receptor antagonist) significantly reduced phagocytosis induced by both venom PLA(2)s. However, Indomethacin (COX-1/COX-2 inhibitor) and Montelukast (CysL receptor antagonist) did not affect the toxins-induced phagocytosis. Moreover, while PACOCF3 (iPLA(2) inhibitor), reduced the phagocytosis induced by MT-II and MT-III, AACOCF3 (cPLA(2) inhibitor) significantly reduced the MT-II, but not MT-Ill-induced phagocytosis. These data suggest the effect of both sPLA(2)s depends on IPLA(2) and that the effect of MT-II depends on activation of cPLA(2). COX-2 and 5-W-derived metabolites as well as PAF are involved in the signaling events required for phagocytosis induced by both venom sPLA(2)s. (C) 2018 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 02/13863-2 - Efeitos dos venenos de Bothrops asper e de Crotalus durissus terrificus, das miotoxinas MT-II e MT-III, crotoxina e crotapotina sobre a liberação de prostanóides e a expressão de ciclooxigenases: estudos in vivo e in vitro
• Beneficiário: Catarina de Fatima Pereira Teixeira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 02/01009-7 - Estudos da sinalização intracelular e proteínas de citoesqueleto no processo de fagocitose por macrófagos induzido por duas toxinas com estrutura de Fosfolipase A2 (mt-ii e MT-III), isoladas no veneno de Bothrops asper
• Beneficiário: Juliana Pavan Zuliani
• Modalidade de apoio: Bolsas no Brasil - Doutorado