title: Increased expression of NTPDases 2 and 3 in mesenteric endothelial cells during schistosomiasis favors leukocyte adhesion through P2Y1 receptors.
abstract: Schistosomiasis is caused by an intravascular parasite and linked to phenotypic changes in endothelial cells that favor inflammation. Endothelial cells express P2Y1 receptors (P2Y1R), and their activation by ADP favors leukocyte adhesion to the endothelial monolayer. We aimed to evaluate the influence of schistosomiasis upon endothelial purinergic signaling-mediated leukocyte adhesion. Mesenteric endothelial cells and mononuclear cells from control and Schistosoma mansoni-infected mice were used in co-culture. P2Y1R levels were similar in both groups. Basal leukocyte adhesion was higher in the infected than in the control group; leukocyte adhesion increased after treatment with the P2Y1R agonist 2-MeSATP in both groups, though it only marginally increased in the infected group. Pre-incubation with the selective P2Y1R antagonist MRS2179 (0.3μM) prevented the agonist effect. However, in the infected group it also reduced the basal leukocyte adhesion, suggesting endothelial cell pre-activation. The endothelial expressions of NTPDases 2 and 3 were significantly increased in the infected group, increasing extracellular ATP hydrolysis and ADP formation by endothelial cells. Therefore, mesenteric endothelial cells are primed by schistosomiasis to a pro-inflammatory phenotype characterized by an increased expression of NTPDases 2 and 3, favoring ADP accumulation and mononuclear cell adhesion, possibly contributing to mesenteric inflammation and schistosomiasis morbidity.
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil.
authors.forename: Suellen Darc Santos
authors.initials: SD
authors.lastname: Oliveira
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil.
authors.forename: Nathália F
authors.initials: NF
authors.lastname: Oliveira
authors.affiliation: Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil.
authors.forename: José R
authors.initials: JR
authors.lastname: Meyer-Fernandes
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil.
authors.forename: Luiz Eduardo Baggio
authors.initials: LE
authors.lastname: Savio
authors.affiliation: Institute of Bioscience, University of São Paulo, 05508-090 São Paulo, SP, Brazil.
authors.forename: Flavia G I
authors.initials: FG
authors.lastname: Ornelas
authors.affiliation: Institute of Bioscience, University of São Paulo, 05508-090 São Paulo, SP, Brazil.
authors.forename: Zulma S
authors.initials: ZS
authors.lastname: Ferreira
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil.
authors.forename: Robson
authors.initials: R
authors.lastname: Coutinho-Silva
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil. Electronic address: cmartins@farmaco.ufrj.br.
authors.forename: Claudia Lucia Martins
authors.initials: CL
authors.lastname: Silva
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000469:parasitology; D054884:Host-Pathogen Interactions; D006801:Humans; D006868:Hydrolysis; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism* / Q000469:parasitology; D008297:Male; D008643:Mesentery / Q000098:blood supply*; D051379:Mice; D010641:Phenotype; D058912:Purinergic P2Y Receptor Agonists / Q000494:pharmacology; D058472:Receptors, Purinergic P2Y1 / Q000187:drug effects / Q000378:metabolism*; D012550:Schistosoma mansoni / Q000472:pathogenicity*; D012552:Schistosomiasis / Q000201:enzymology* / Q000469:parasitology; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: C546383:P2ry1 protein, mouse; D058912:Purinergic P2Y Receptor Agonists; D058472:Receptors, Purinergic P2Y1; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C027201:ectoATPase
keywords: Endothelial cells; NTPDases; P2Y1 receptors; Purinergic signaling; Schistosoma mansoni