Increased expression of NTPDases 2 and 3 in mesenteric endothelial cells during schistosomiasis favors leukocyte adhesion through P2Y₁ receptors

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• 作者：Suellen Darc Santos Oliveira^a ; ^b ; ¹ ; Nathá ; lia F. Oliveira^b ; José ; R. Meyer-Fernandes^c ; Luiz Eduardo Baggio Savio^b ; Flavia G.I. Ornelas^d ; Zulma S. Ferreira^d ; Robson Coutinho-Silva^a ; Claudia Lucia Martins Silva^b ; ^{cmartins@farmaco.ufrj.br" class="auth_mail" title="E-mail the corresponding author}
• 关键词：CPM ; counts per minute ; DAMP ; damage-associated molecular pattern ; E-NTPDase ; ecto-nucleoside triphosphate diphosphohydrolase ; HPLC ; high performance liquid chromatography ; LPS ; lipopolysaccharide ; NOS ; nitric oxide synthase
• 刊名：Vascular Pharmacology
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：82
• 期：Complete
• 页码：66-72
• 全文大小：591 K

文摘

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 (0.3 μM) 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.