Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/6635
Title: Endothelin-1 receptors play a minor role in the protection against acute Trypanosoma cruzi infection in mice
Authors: Roffê, Ester
Souza, Adriano Luís Soares de
Machado, P. P.
Barcelos, L. S.
Romanha, Álvaro José
Mariano, F.S.
Silva, J. S.
Machado, C. R.
Tanowitz, H. B.
Teixeira, Mauro Martins
Affilliation: Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil
Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Bioquímica e Imunologia. Ribeirão Preto, SP, Brasil
Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Bioquímica e Imunologia. Ribeirão Preto, SP, Brasil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Belo Horizonte, MG, Brasil
Albert Einstein College of Medicine. Bronx, NY, USA/Montefiore Medical Center. Bronx, NY, USA
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil
Abstract: Chagas’ disease, caused by the protozoan Trypanosoma cruzi, is a major cause of cardiovascular disability in countries where it is endemic. Damage to the heart microvasculature has been proposed to be an important factor in the pathogenesis of heart dysfunction. Endothelin-1 (ET-1) is a potent vasoconstrictor and exerts its effects via specific ETAand ETBreceptors. A few studies have suggested a role for ET-1 and its receptors in the pathogenesis of Chagas’ disease. We investigated the effects of treatment with bosentan, an ETA/ETB receptor antagonist, on the course of T. cruzi infection (Y strain) in C57Bl/6 mice. Treatment with bosentan (100 mg kg-1 day -1 ) was given per osstarting day 0 after infection until sacrifice. Bosentan signifi-cantly increased myocardial inflammation, with no effects on parasi-temia. Although the total number of nests was similar, a lower number of intact amastigote nests was found in the heart of bosentan-treated animals. Bosentan failed to affect the infection-associated increase in the cardiac levels of the cytokines IFN-γand TNF-αand the chemo-kines CCL2/MCP-1, CCL3/MIP-1αand CCL5/RANTES. In vitro, pre-incubation with ET-1 (0.1 µM) 4 h before infection enhanced the uptake of the parasites by peritoneal macrophages, and this effect was abrogated when macrophages were pre-treated with bosentan (1 µM) 15 min before incubation with ET-1. However, ET-1 did not alter killing of intracellular parasites after 48 h of in vitroinfection. Our data suggest that bosentan-treated mice have a delay in controlling parasitism which is compensated for exacerbated inflammation. In-fection is eventually controlled in these animals and lethality is unchanged, demonstrating that ET-1 plays a minor role in the protec-tion against acute murine T. cruziinfection.
Keywords: Trypanosoma cruzi
Endothelin
Myocarditis Chemokines
Issue Date: 2007
Citation: Roffê, E et al. Endothelin-1 receptors play a minor role in the protection against acute Trypanosoma cruzi infection in mice. Braz J Med Biol Res. 2007 Mar;40(3):391-9.
ISSN: 0100-879X
Copyright: open access
Appears in Collections:MG - IRR - Artigos de Periódicos

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