A Snake Venom-Secreted Phospholipase A 2 Induces Foam Cell Formation Depending on the Activation of Factors Involved in Lipid Homeostasis

• Published in: Mediators of inflammation 2018-06, Vol.2018, p.1-13
• Main Authors: Leiguez, Elbio, Giannotti, Karina Cristina, Viana, Mariana do Nascimento, Matsubara, Márcio Hideki, Fernandes, Cristina Maria, Gutiérrez, José Maria, Lomonte, Bruno, Teixeira, Catarina
• Format: Article
• Language: English
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2018/2547918

MT-III, a snake venom GIIA sPLA 2 , which shares structural and functional features with mammalian GIIA sPLA 2 s, activates macrophage defense functions including lipid droplet (LDs) formation, organelle involved in both lipid metabolism and inflammatory processes. Macrophages (M Φ s) loaded with LDs, termed foam cells, characterize early blood vessel fatty-streak lesions during atherosclerosis. However, the factors involved in foam cell formation induced by a GIIA sPLA 2 are still unknown. Here, we investigated the participation of lipid homeostasis-related factors in LD formation induced by MT-III in macrophages. We found that MT-III activated PPAR- γ and PPAR- β / δ and increased the protein levels of both transcription factors and CD36 in macrophages. Pharmacological interventions evidenced that PPAR- γ , PPAR- β / δ , and CD36 as well as the endoplasmic reticulum enzymes ACAT and DGAT are essential for LD formation. Moreover, PPAR- β / δ , but not PPAR- γ , is involved in MT-III-induced PLIN2 protein expression, and both PPAR- β/δ and PPAR- γ upregulated CD36 protein expression, which contributes to MT-III-induced COX-2 expression. Furthermore, production of 15-d-PGJ 2 , an activator of PPARs, induced by MT-III, was dependent on COX-1 being LDs an important platform for generation of this mediator.