Journal
JOURNAL OF CELL COMMUNICATION AND SIGNALING
Volume 14, Issue 1, Pages 111-126Publisher
SPRINGER
DOI: 10.1007/s12079-019-00540-8
Keywords
Purinergic signaling; T lymphocytes; ADP-receptor P2Y(12); P2Y(12) antagonist
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Funding
- American Heart Association [16SDG26980003]
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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 P2Y(12) 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 P2Y(12) agonist), AR-C69931MX (a P2Y(12) 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 P2Y(12)-dependent and P2Y(12)-independent pathways and other responses (cytokine secretion) primarily through P2Y(12) -independent pathways. The ADP-mediated effect changed over time and was stimulus-specific.
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