A group IIA-secreted phospholipase A(2) from snake venom induces lipid body formation in macrophages: the roles of intracellular phospholipases A(2) and distinct signaling pathways

Autor(es)

Leiguez, Elbio ^[1] ; Zuliani, Juliana Pavan ; Cianciarullo, Aurora Marques ^[2] ; Fernandes, Cristina Maria ^[1] ; Maria Gutierrez, Jose ^[3] ; Teixeira, Catarina ^[1]

Afiliação do(s) autor(es)

^[1] Inst Butantan, Farmacol Lab, BR-05503900 Sao Paulo - Brazil

^[2] Inst Butantan, Genet Lab, BR-05503900 Sao Paulo - Brazil

^[3] Univ Costa Rica, Inst Clodomiro Picado, San Pedro - Costa Rica

• Tipo de documento: Artigo Científico
• Fonte: Journal of Leukocyte Biology; v. 90, n. 1, p. 155-166, JUL 2011.
• Citações Web of Science: 13

Resumo

We investigated the ability of the sPLA(2), known as MT-III, isolated from the viperid snake Bothrops asper, to induce LB formation in macrophages and the major cellular signaling pathways involved in this process. The effects of MT-III on ADRP localization and expression and macrophage ultrastructure were assessed. Our results showed that this sPLA(2) induced a marked increase in LB numbers in macrophages, induced the recruitment of ADRP in macrophages, and up-regulated ADRP expression. Ultrastructural analysis showed the presence of weakly and strongly osmiophilic LBs in sPLA(2)-stimulated cells. Enlargement of the ER and Golgi cisterns was also observed. Pretreatment of cells with H7 or staurosporine (PKC inhibitors), LY294002 or wortmannin (PI3K inhibitors), SB202190 or PD98059 (p38(MAPK) and ERK1/2 inhibitors, respectively), or Pyr-2 or Bel (cPLA(2) and iPLA(2) inhibitors, respectively) significantly reduced sPLA(2)-induced LB formation. Herbimycin (a PTK inhibitor) and indomethacin or etoricoxib (COX inhibitors) failed to alter sPLA(2)-induced effects. In conclusion, our results show for the first time the ability of a venom sPLA(2) to induce the formation of LBs and the expression of ADRP in macrophages. Venom PLA(2)-induced LB formation is dependent on PKC, PI3K, p38(MAPK), ERK1/2, cPLA(2), and iPLA(2) signaling pathways but not on PTK, COX-1, or COX-2 pathways. Activation of the ER and Golgi complex may play an important role in the formation of LBs induced by this sPLA(2) in macrophages. J. Leukoc. Biol. 90: 155-166; 2011. (AU)

• Processo FAPESP: 06/58334-8 - Mecanismos intracelulares envolvidos na formação de corpúsculos lipídicos induzida por uma toxina com estrutura de fosfolipase A2 (MT-III), isolada do veneno da serpente Bothrops asper, em macrófagos
• Beneficiário: Elbio Leiguez Junior
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 08/58988-3 - Estudos dos mecanismos moleculares envolvidos na síntese de prostaglandina E2, induzida pela metaloproteinase BAP1, em fibroblastos sinoviais em cultura: expressão diferencial de genes e das enzimas ciclooxigenase-2 e PGE sintase microssomal-1
• Beneficiário: Cristina Maria Fernandes
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado