Endothelial P2X7 receptors’ expression is reduced by schistosomiasis
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Endothelial cells control vascular tone, permeability and leukocyte transmigration and are modulated by pro-inflammatory mediators. Schistosomiasis is an intravascular disease associated with inflammation, therefore altering endothelial cells’ phenotype. Purinergic P2X7 receptors (P2X7R) play an important role in inflammation; however, the impact of the disease upon endothelial P2X7R function or expression has not been explored. Using ethidium bromide uptake to investigate P2X7R function, we observed that the effects of ATP (3 mM) and the P2X7R agonist 3′-O-(4-benzoyl)-ATP (BzATP) were smaller in mesenteric endothelial cells from the Schistosoma mansoni-infected group than in the control group. In the control group, BzATP induced endothelial nitric oxide production, which was blocked by the P2X7R antagonists KN-62 and A740003. However, in the infected group, we observed a reduced effect of BzATP and no effect of both P2X7R antagonists, suggesting a downregulation of endothelial P2X7R in schistosomiasis. We observed similar results in both infected and P2X7R−/− groups, which were also comparable to data obtained with KN-62- or A740004-treated control cells. Data from Western blot and immunocytochemistry assays confirmed the reduced expression of P2X7R in the infected group. In conclusion, our data show a downregulation of P2X7R in schistosomiasis infection, which likely limits the infection-related endothelial damage.
KeywordsP2X7 receptors Endothelial cells Schistosoma mansoni Nitric oxide Murine
The authors thank Dr. Silvana Aparecida Rogel Carvalho Thiengo (FIOCRUZ, Rio de Janeiro, Brazil) for the cercariae donation. This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil (www.cnpq.br) financial support (472474/2010-3) and fellowship (Suellen D´arc dos Santos Oliveira, Claudia Lucia Martins da Silva and Robson Coutinho Silva); Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Programa de Núcleos de Excelência (PRONEX-CNPq) and Instituto Nacional para Pesquisa Translacional em Saúde e Ambiente na Região Amazônica, Conselho Nacional de Desenvolvimento Científico e Tecnológico/MCT (INCT-INPeTAm/CNPq/MCT), Brazil. The funder had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
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