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 Artículo académico Profesión de escritor uri icon

Abstracto

  • We investigated the ability of the sPLA2, 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 sPLA2 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 sPLA2-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 (p38MAPK and ERK1/2 inhibitors, respectively), or Pyr-2 or Bel (cPLA2 and iPLA2 inhibitors, respectively) significantly reduced sPLA2-induced LB formation. Herbimycin (a PTK inhibitor) and indomethacin or etoricoxib (COX inhibitors) failed to alter sPLA2-induced effects. In conclusion, our results show for the first time the ability of a venom sPLA2 to induce the formation of LBs and the expression of ADRP in macrophages. Venom PLA2-induced LB formation is dependent on PKC, PI3K, p38MAPK, ERK1/2, cPLA2, and iPLA2 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 sPLA2 in macrophages.

fecha de publicación

  • 2011