1. Increased expression of NTPDases 2 and 3 in mesenteric endothelial cells during schistosomiasis favors leukocyte adhesion through P2Y1 receptors.
- Author
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Oliveira SD, Oliveira NF, Meyer-Fernandes JR, Savio LE, Ornelas FG, Ferreira ZS, Coutinho-Silva R, and Silva CL
- Subjects
- Adenosine Diphosphate metabolism, Adenosine Triphosphate metabolism, Animals, Cells, Cultured, Coculture Techniques, Disease Models, Animal, Endothelial Cells drug effects, Endothelial Cells parasitology, Host-Pathogen Interactions, Humans, Hydrolysis, Leukocytes drug effects, Leukocytes parasitology, Male, Mice, Phenotype, Purinergic P2Y Receptor Agonists pharmacology, Receptors, Purinergic P2Y1 drug effects, Schistosomiasis parasitology, Signal Transduction, Up-Regulation, Adenosine Triphosphatases metabolism, Cell Adhesion, Endothelial Cells enzymology, Leukocytes metabolism, Mesentery blood supply, Receptors, Purinergic P2Y1 metabolism, Schistosoma mansoni pathogenicity, Schistosomiasis enzymology
- 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., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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