Cargando…
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
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 phospholip...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875421/ https://www.ncbi.nlm.nih.gov/pubmed/31781674 http://dx.doi.org/10.1155/2019/2745286 |
_version_ | 1783473027506241536 |
---|---|
author | de Carvalho, Ana Eduarda Zulim Giannotti, Karina Junior, Elbio Leiguez Matsubara, Márcio Santos, Maria Cristina Dos Fortes-Dias, Consuelo Latorre Teixeira, Catarina |
author_facet | de Carvalho, Ana Eduarda Zulim Giannotti, Karina Junior, Elbio Leiguez Matsubara, Márcio Santos, Maria Cristina Dos Fortes-Dias, Consuelo Latorre Teixeira, Catarina |
author_sort | de Carvalho, Ana Eduarda Zulim |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6875421 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-68754212019-11-28 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 de Carvalho, Ana Eduarda Zulim Giannotti, Karina Junior, Elbio Leiguez Matsubara, Márcio Santos, Maria Cristina Dos Fortes-Dias, Consuelo Latorre Teixeira, Catarina J Immunol Res Research Article 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. Hindawi 2019-11-04 /pmc/articles/PMC6875421/ /pubmed/31781674 http://dx.doi.org/10.1155/2019/2745286 Text en Copyright © 2019 Ana Eduarda Zulim de Carvalho et al. http://creativecommons.org/licenses/by/4.0/ 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. |
spellingShingle | Research Article de Carvalho, Ana Eduarda Zulim Giannotti, Karina Junior, Elbio Leiguez Matsubara, Márcio Santos, Maria Cristina Dos Fortes-Dias, Consuelo Latorre Teixeira, Catarina 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 |
title |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_short |
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 |
title_sort | 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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875421/ https://www.ncbi.nlm.nih.gov/pubmed/31781674 http://dx.doi.org/10.1155/2019/2745286 |
work_keys_str_mv | AT decarvalhoanaeduardazulim crotalusdurissusruruimasnakevenomandaphospholipasea2isolatedfromthisvenomelicitmacrophagestoformlipiddropletsandsynthesizeinflammatorylipidmediators AT giannottikarina crotalusdurissusruruimasnakevenomandaphospholipasea2isolatedfromthisvenomelicitmacrophagestoformlipiddropletsandsynthesizeinflammatorylipidmediators AT juniorelbioleiguez crotalusdurissusruruimasnakevenomandaphospholipasea2isolatedfromthisvenomelicitmacrophagestoformlipiddropletsandsynthesizeinflammatorylipidmediators AT matsubaramarcio crotalusdurissusruruimasnakevenomandaphospholipasea2isolatedfromthisvenomelicitmacrophagestoformlipiddropletsandsynthesizeinflammatorylipidmediators AT santosmariacristinados crotalusdurissusruruimasnakevenomandaphospholipasea2isolatedfromthisvenomelicitmacrophagestoformlipiddropletsandsynthesizeinflammatorylipidmediators AT fortesdiasconsuelolatorre crotalusdurissusruruimasnakevenomandaphospholipasea2isolatedfromthisvenomelicitmacrophagestoformlipiddropletsandsynthesizeinflammatorylipidmediators AT teixeiracatarina crotalusdurissusruruimasnakevenomandaphospholipasea2isolatedfromthisvenomelicitmacrophagestoformlipiddropletsandsynthesizeinflammatorylipidmediators |