Bothrops jararaca snake venom inflammation induced in human whole blood: role of the complement system

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dc.contributor(LBI) Laboratório de Imunoquímicapt_BR
dc.contributorPrograma de Pós-Graduação em Ciências – Toxinologia (PPGTox)pt_BR
dc.contributor.authorLeonel, Thyago Bispopt_BR
dc.contributor.authorGabrili, Joel José Megalept_BR
dc.contributor.authorSquaiella-Baptistão, Carla Cristinapt_BR
dc.contributor.authorWoodruff, Trent M.pt_BR
dc.contributor.authorLambris, John D.pt_BR
dc.contributor.authorTambourgi, Denise Vilarinhopt_BR
dc.identifier.citationLeonel TB, Gabrili JJM, Squaiella-Baptistão CC, Woodruff TM., Lambris JD., Tambourgi DV. Bothrops jararaca snake venom inflammation induced in human whole blood: role of the complement system. Front. Immunol. 2022 June;13:885223. doi:10.3389/fimmu.2022.885223.pt_BR
dc.description.abstractThe clinical manifestations of envenomation by Bothrops species are complex and characterized by prominent local effects that can progress to tissue loss, physical disability, or amputation. Systemic signs can also occur, such as hemorrhage, coagulopathy, shock, and acute kidney failure. The rapid development of local clinical manifestations is accompanied by the presence of mediators of the inflammatory process originating from tissues damaged by the bothropic venom. Considering the important role that the complement system plays in the inflammatory response, in this study, we analyzed the action of Bothrops jararaca snake venom on the complement system and cell surface receptors involved in innate immunity using an ex vivo human whole blood model. B. jararaca venom was able to induce activation of the complement system in the human whole blood model and promoted a significant increase in the production of anaphylatoxins C3a/C3a-desArg, C4a/C4a-desArg, C5a/C5a-desArg and sTCC. In leukocytes, the venom of B. jararaca reduced the expression of CD11b, CD14 and C5aR1. Inhibition of the C3 component by Cp40, an inhibitor of C3, resulted in a reduction of C3a/C3a-desArg, C5a/C5a-desArg and sTCC to basal levels in samples stimulated with the venom. Exposure to B. jararaca venom induced the production of inflammatory cytokines and chemokines such as TNF-α, IL-8/CXCL8, MCP-1/CCL2 and MIG/CXCL9 in the human whole blood model. Treatment with Cp40 promoted a significant reduction in the production of TNF-α, IL-8/CXCL8 and MCP-1/CCL2. C5aR1 inhibition with PMX205 also promoted a reduction of TNF-α and IL-8/CXCL8 to basal levels in the samples stimulated with venom. In conclusion, the data presented here suggest that the activation of the complement system promoted by the venom of the snake B. jararaca in the human whole blood model significantly contributes to the inflammatory process. The control of several inflammatory parameters using Cp40, an inhibitor of the C3 component, and PMX205, a C5aR1 antagonist, indicates that complement inhibition may represent a potential therapeutic tool in B. jararaca envenoming.pt_BR
dc.description.sponsorship(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulopt_BR
dc.description.sponsorship(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológicopt_BR
dc.relation.ispartofFrontiers in Immunologypt_BR
dc.rightsOpen accesspt_BR
dc.titleBothrops jararaca snake venom inflammation induced in human whole blood: role of the complement systempt_BR
dc.rights.licenseCC BYpt_BR
dc.contributor.external(UQ) University of Queenslandpt_BR
dc.contributor.externalUniversity of Pennsylvaniapt_BR
dc.subject.keywordhuman whole bloodpt_BR
dc.subject.keywordcomplement system and inhibitorspt_BR
dc.subject.keywordBothrops jararacapt_BR
dc.subject.keywordsnake venompt_BR
dc.relation.ispartofabbreviatedFront. Immunolpt_BR
dc.identifier.citationabntv. 13, 885223, jun. 2022pt_BR
dc.identifier.citationvancouver2022 June;13:885223pt_BR
dc.contributor.butantanLeonel, Thyago Bispo|:Aluno:(LBI) Laboratório de Imunoquímica:Programa de Pós-Graduação em Ciências – Toxinologia (PPGTox)|:PrimeiroAutorpt_BR
dc.contributor.butantanGabrili, Joel José Megale|:Desvinculado|:(LBI) Laboratório de Imunoquímicapt_BR
dc.contributor.butantanSquaiella-Baptistão, Carla Cristina|:Pesquisador|:(LBI) Laboratório de Imunoquímicapt_BR
dc.contributor.butantanTambourgi, Denise Vilarinho|:Pesquisador:Docente permanente PPGTox|:(LBI) Laboratório de Imunoquímica|:Autor de correspondênciapt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2013/07467-1pt_BR
dc.sponsorship.butantan(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico¦¦pt_BR
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