A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ(2) in macrophages

Author(s)

Giannotti, Karina Cristina ; Leiguez, Elbio ; Zulim de Carvalho, Ana Eduarda ; Nascimento, Neide Galvao ; Matsubara, Marcio Hideki ; Fortes-Dias, Consuelo Latorre ; Moreira, Vanessa ; Teixeira, Catarina

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 7, JUN 22 2017.
• Web of Science Citations: 4

Abstract

Crotoxin B (CB) is a catalytically active group IIA sPLA(2) from Crotalus durissus terrificus snake venom. In contrast to most GIIA sPLA(2)s, CB exhibits anti-inflammatory effects, including the ability to inhibit leukocyte functions. Lipid droplets (LDs) are lipid-rich organelles associated with inflammation and recognized as a site for the synthesis of inflammatory lipid mediators. Here, the ability of CB to induce formation of LDs and the mechanisms involved in this effect were investigated in isolated macrophages. The profile of CB-induced 15-d-PGJ(2) (15-Deoxy-Delta-12,14-prostaglandin J2) production and involvement of LDs in 15-d-PGJ(2) biosynthesis were also investigated. Stimulation of murine macrophages with CB induced increased number of LDs and release of 15-d-PGJ(2). LDs induced by CB were associated to PLIN2 recruitment and expression and required activation of PKC, PI3K, MEK1/2, JNK, iPLA2 and PLD. Both 15-d-PGJ(2) and COX-1 were found in CB-induced LDs indicating that LDs contribute to the inhibitory effects of CB by acting as platform for synthesis of 15-d-PGJ(2), a proresolving lipid mediator. Together, our data indicate that an immunomodulatory GIIA sPLA(2) can directly induce LD formation and production of a pro-resolving mediator in an inflammatory cell and afford new insights into the roles of LDs in resolution of inflammatory processes. (AU)

• FAPESP's process: 13/22610-5 - Studies on the effects of a phospholipase A2 isolated from Bothrops asper snake venom on smooth muscle vascular cells in culture. Formation of Lipid Droplets and mechanisms involved in this effect.
• Grantee: Karina Cristina Giannotti
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 08/57898-0 - National Institute of Science and Technology on Toxins
• Grantee: Osvaldo Augusto Brazil Esteves Sant'Anna
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 11/21341-5 - Studies on the mechanisms involved in lipid body formation induced by a snake venom phospholipase A2 in isolated macrophages: participation of lipid homeosthasis factors
• Grantee: Catarina de Fatima Pereira Teixeira
• Support type: Regular Research Grants