Research Article Crotalus durissus ruruima Snake Venom and a Phospholipase A 2 Isolated from This Venom Elicit Macrophages to Form Lipid Droplets and Synthesize Inflammatory Lipid Mediators Ana Eduarda Zulim de Carvalho , 1 Karina Giannotti, 1 Elbio Leiguez Junior, 1 Márcio Matsubara, 1 Maria Cristina Dos Santos, 2 Consuelo Latorre Fortes-Dias, 3 and Catarina Teixeira 1 1 Butantan Institute, São Paulo, São Paulo, Brazil 2 Departamento de Ciências Fisiológicas, Universidade do Amazonas, Manaus, Brazil 3 Fundação Ezequiel Dias, Belo Horizonte, Minas Gerais, Brazil Correspondence should be addressed to Catarina Teixeira; catarina.teixeira@butantan.gov.br Received 28 December 2018; Revised 13 May 2019; Accepted 3 September 2019; Published 4 November 2019 Academic Editor: Benoit Stijlemans Copyright © 2019 Ana Eduarda Zulim de Carvalho et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Viper snake Crotalus durissus ruruima (Cdr) is a subspecies found in northern area of Brazil. Among the snakes of Crotalus genus subspecies, the venom of Cdr presents highest level of crotoxin, which is the major component of Crotalus snake venoms, formed by two subunits (crotapotin and a phospholipase A 2 named CBr) and presents potent neurotoxic activity. Curiously, the venom of C. d. ruruima (CdrV) is better neutralized by antibothropic than by anticrotalic serum, strongly suggesting that this venom has similarities with venom of Bothrops genus snakes with regard to the ability to induce inflammation. Macrophages are cells with a central role in inflammatory and immunological responses. Upon inflammatory stimuli, these cells exhibit increased numbers of lipid droplets, which are key organelles in the synthesis and release of inflammatory mediators. However, the effects of CdrV and CBr in macrophage functions are unknown. We herein investigated the ability of CdrV and CBr to activate macrophages with focus on the formation of lipid droplets (LDs), synthesis of lipid mediators, and mechanisms involved in these effects. The involvement of LDs in PGE 2 biosynthesis was also assessed. Stimulation of murine macrophages with CdrV and CBr induced an increased number of LDs and release of prostanoids (PGE 2 , PGD 2 , and TXB 2 ). Neither CdrV nor CBr induced the expression of COX-1 and COX-2 by macrophages. LDs induced by both CdrV and CBr are associated to PLIN2 recruitment and expression and were shown to be dependent on COX-1, but not COX-2 activity. Moreover, PGE 2 colocalized to CdrV- and CBr-induced LDs, revealing the role of these organelles as sites for the synthesis of prostanoids. These results evidence, for the first time, the ability of a whole snake venom to induce formation of LDs and the potential role of these organelles for the production of inflammatory mediators during envenomation by Crotalus snakes. 1. Introduction Snake venoms of the Viperidae family are largely recognized to induce proinflammatory reactions during envenomation [1]. However, as an exception, venoms from Crotalus genus snakes exert potent neurotoxic effects, do not induce inflam- matory responses in their victims, and have been reported as negative modulators of the inflammatory response both in vivo and in vitro experimental conditions [2–5]. Crotalus durissus are venomous rattlesnakes found in the Americas with many subspecies irregularly distributed throughout the continent [6]. The major toxic and lethal effects of Crotalus durissus ssp. venoms are associated to cro- toxin, a heterodimer toxin composed by the noncovalent association of a basic subunit (CB), comprising a phospholi- pase A 2 (PLA 2 ), and an acidic subunit that lacks enzymatic activity known as CA or crotapotin [7–10]. The CB subunit from Crotalus durissus terrificus snake venom is responsible Hindawi Journal of Immunology Research Volume 2019, Article ID 2745286, 12 pages https://doi.org/10.1155/2019/2745286