Role of the complement system in kidney cell death induced by Loxosceles venom Sphingomyelinases D

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dc.contributor(LBI) Lab. Imunoquímicapt_BR
dc.contributor.authorOkamoto, Cinthya Kimoript_BR
dc.contributor.authorBerg, Carmen W. van denpt_BR
dc.contributor.authorPohl, Paula Cristianept_BR
dc.contributor.authorTambourgi, Denise Vilarinhopt_BR
dc.description.abstractEnvenomation by Loxosceles spiders can result in local and systemic pathologies. Systemic loxoscelism, which can lead to death, is characterized by intravascular hemolysis, platelet aggregation, and acute kidney injury. Sphingomyelinase D (SMase D) in Loxosceles spider venom is responsible for both local and systemic pathologies, and has been shown to induce metalloprotease activity. As the complement system is involved in many renal pathologies and is involved in hemolysis in systemic loxoscelism, the aim of this study was to investigate its role and the role of complement regulators and metalloproteases in an in vitro model of Loxosceles venom induced renal pathology. We investigated the effects of the venom/SMase D and the complement system on the HK-2 kidney cell line. Using cell viability assays, western blotting, and flow cytometry, we show that human serum, as a source of complement, enhanced the venom/SMase D induced cell death and the deposition of complement components and properdin. Inhibitors for ADAM-10 and ADAM-17 prevented the venom induced release of the of the complement regulator MCP/CD46 and reduced the venom/SMase D induced cell death. Our results show that the complement system can contribute to Loxosceles venom induced renal pathology. We therefore suggest that patients experiencing systemic loxoscelism may benefit from treatment with metalloproteinase inhibitors and complement inhibitors, but this proposition should be further analyzed in future pre-clinical and clinical assays.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.ispartofArchives of Toxicologypt_BR
dc.rightsRestricted accesspt_BR
dc.titleRole of the complement system in kidney cell death induced by Loxosceles venom Sphingomyelinases Dpt_BR
dc.contributor.externalCardiff Universitypt_BR
dc.subject.keywordComplement Systempt_BR
dc.subject.keywordKidney cellspt_BR
dc.subject.keywordLoxosceles spider venompt_BR
dc.subject.keywordSphingomyelinase Dpt_BR
dc.subject.keywordSystemic loxoscelismpt_BR
dc.relation.ispartofabbreviatedArch Toxicolpt_BR
dc.identifier.citationabntv. 98, p. 1561-1572, 2024pt_BR
dc.identifier.citationvancouver2024; 98:1561-1572pt_BR
dc.contributor.butantanTambourgi, Denise Vilarinho|:Pesquisador|:(LBI) Lab. 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¦¦308390/2021-0pt_BR
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