title: Macrophage P2X7 receptor function is reduced during schistosomiasis: putative role of TGF- β1.
abstract: Schistosomiasis is a chronic inflammatory disease whose macrophages are involved in immunopathology modulation. Although P2X7 receptor signaling plays an important role in inflammatory responses mediated by macrophages, no reports have examined the role of P2X7 receptors in macrophage function during schistosomiasis. Thus, we evaluated P2X7 receptor function in peritoneal macrophages during schistosomiasis using an ATP-induced permeabilization assay and measurements of the intracellular Ca(2+) concentration. ATP treatment induced significantly less permeabilization in macrophages from S. mansoni-infected mice than in control cells from uninfected animals. Furthermore, P2X7-mediated increases in intracellular Ca(2+) levels were also reduced in macrophages from infected mice. TGF-β1 levels were increased in the peritoneal cavity of infected animals, and pretreatment of control macrophages with TGF-β1 reduced ATP-induced permeabilization, mimicking the effect of S. mansoni infection. Western blot and qRT-PCR data showed no difference in P2X7 protein and mRNA between uninfected, infected, and TGF-β1-treated groups. However, immunofluorescence analysis revealed reduced cell surface localization of P2X7 receptors in macrophages from infected and TGF-β1-treated mice compared to controls. Therefore, our data suggest that schistosomiasis reduces peritoneal macrophage P2X7 receptor signaling. This effect is likely due to the fact that infected mice have increased levels of TGF-β1, which reduces P2X7 receptor cell surface expression.
authors.affiliation: Laboratory of Immunophysiology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil ; Laboratory of Molecular and Biochemical Pharmacology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, 21941-599 Rio de Janeiro, RJ, Brazil ; National Institute of Translational Research in Health and Environment in the Amazon Region, Rio de Janeiro, Brazil.
authors.forename: Suellen D'arc Santos
authors.initials: SD
authors.lastname: Oliveira
authors.affiliation: Laboratory of Immunophysiology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Hayandra Ferreira
authors.initials: HF
authors.lastname: Nanini
authors.affiliation: Laboratory of Immunophysiology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil ; National Institute of Translational Research in Health and Environment in the Amazon Region, Rio de Janeiro, Brazil.
authors.forename: Luiz Eduardo Baggio
authors.initials: LE
authors.lastname: Savio
authors.affiliation: Laboratory for Functional Genomics and Bioinformatics, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Mariana Caldas
authors.initials: MC
authors.lastname: Waghabi
authors.affiliation: Laboratory of Molecular and Biochemical Pharmacology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, 21941-599 Rio de Janeiro, RJ, Brazil.
authors.forename: Claudia Lucia Martins
authors.initials: CL
authors.lastname: Silva
authors.affiliation: Laboratory of Immunophysiology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil ; National Institute of Translational Research in Health and Environment in the Amazon Region, Rio de Janeiro, Brazil ; Instituto de Biofisica Carlos Chagas Filho, UFRJ, Edifício do Centro de Ciências da Saúde, Bloco G., Avenida Carlos Chagas Filho 373, Cidade Universitária, Ilha do Fundão, 21941-902 Rio de Janeiro, RJ, Brazil.
authors.forename: Robson
authors.identifier: 0000-0002-7318-0204
authors.initials: R
authors.lastname: Coutinho-Silva
mesh_terms: D000818:Animals; D015153:Blotting, Western; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012552:Schistosomiasis / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D058486:Receptors, Purinergic P2X7; D053773:Transforming Growth Factor beta1