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ADP exerts P2Y 12 -dependent and P2Y 12 -independent effects on primary human T cell responses to stimulation
Journal of Cell Communication and Signaling ( IF 3.6 ) Pub Date : 2019-12-05 , DOI: 10.1007/s12079-019-00540-8
Harika Vemulapalli 1 , Samara Albayati 1 , Viren C Patwa 2 , Douglas G Tilley 2 , Alexander Y Tsygankov 1, 3 , Elisabetta Liverani 1
Affiliation  

Purinergic signaling plays a complex role in inflammation. Nucleotides released by T lymphocytes, endothelial cells, and platelets during inflammation induce cellular responses by binding to receptors that regulate intracellular signaling pathways. Previous studies have found that purinergic signaling can have both proinflammatory and anti-inflammatory effects, but the roles of specific pathways in specific cell types are poorly understood. We investigated the role of the P2Y12 signaling pathway in the activation of T lymphocytes in vitro. We isolated peripheral blood mononuclear cells (PBMCs) from healthy donors and pretreated them with ADP (a P2Y12 agonist), AR-C69931MX (a P2Y12 antagonist), or both. We then stimulated PBMC using phytohemagglutinin (PHA) or anti-CD3/CD28 antibodies. We found that ADP affects T cell responses in term of cell activity and receptor expression through both P2Y12-dependent and P2Y12-independent pathways and other responses (cytokine secretion) primarily through P2Y12 -independent pathways. The ADP-mediated effect changed over time and was stimulus-specific.

中文翻译:

ADP对人类原代T细胞对刺激的反应发挥P2Y 12依赖性和P2Y 12依赖性

嘌呤能信号在炎症中起着复杂的作用。在炎症过程中,T淋巴细胞,内皮细胞和血小板释放的核苷酸通过与调节细胞内信号传导途径的受体结合而诱导细胞反应。先前的研究发现嘌呤能信号传导既具有促炎作用又具有抗炎作用,但是对特定途径在特定细胞类型中的作用了解甚少。我们调查了P2Y 12信号通路在体外激活T淋巴细胞中的作用。我们从健康供体中分离出外周血单核细胞(PBMC),并用ADP(P2Y 12激动剂),AR-C69931MX(P2Y 12拮抗剂),或两者兼而有之。然后,我们使用植物血凝素(PHA)或抗CD3 / CD28抗体刺激PBMC。我们发现,通过ADP既P2Y影响细胞活性和受体的表达的术语T细胞应答12依赖性和P2Y 12非依赖性途径和其他反应(细胞因子分泌)主要通过P2Y 12非依赖性途径。ADP介导的作用随时间改变,并且是刺激特异性的。
更新日期:2019-12-05
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