A2A receptors in inflammation and injury: lessons learned from transgenic animals

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Abstract
Adenosine regulates the function of the innate and adaptive immune systems through targeting virtually every cell type that is involved in orchestrating an immune/inflammatory response. Of the four adenosine receptors (A1, A2A, A2B, A3), A2A receptors have taken center stage as the primary anti-inflammatory effectors of extracellular adenosine. This broad, anti-inflammatory effect of A2A receptor activation is a result of the predominant expression of A2A receptors on monocytes/macrophages, dendritic cells, mast cells, neutrophils, endothelial cells, eosinophils, epithelial cells, as well as lymphocytes, NK cells, and NKT cells. A2A receptor activation inhibits early and late events occurring during an immune response, which include antigen presentation, costimulation, immune cell trafficking, immune cell proliferation, proinflammatory cytokine production, and cytotoxicity. In addition to limiting inflammation, A2A receptors participate in tissue remodeling and reparation. Consistent with their multifaceted, immunoregulatory action on immune cells, A2A receptors have been shown to impact the course of a wide spectrum of ischemic, autoimmune, infectious, and allergic diseases. Here, we review the regulatory roles of A2A receptors in immune/inflammatory diseases of various organs, including heart, lung, gut, liver, kidney, joints, and brain, as well as the role of A2A receptors in regulating multiple organ failure and sepsis.
Funding Information
  • National Institutes of Health (R01 GM66189)
  • Intramural Research Program of NIH
  • National Institute on Alcohol Abuse and Alcoholism
  • Hungarian Research Fund OTKA (T 049537)
  • Hungarian National R&D Program (1A/036/2004)