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Published online before print December 26, 2007

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(Journal of Leukocyte Biology. 2008;83:447-455.)
© 2008 by Society for Leukocyte Biology

A_2A receptors in inflammation and injury: lessons learned from transgenic animals

György Haskó^*,,1 and Pál Pacher

^* Department of Surgery, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey, USA;
Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary; and
Section on Oxidative Stress and Tissue Injury, Laboratory of Physiological Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA

¹Correspondence: Department of Surgery, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, University Heights, Newark, NJ 07103, USA. E-mail: haskoge{at}umdnj.edu

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, A_2A, A_2B, A₃), A_2A receptors have taken center stage as the primary anti-inflammatory effectors of extracellular adenosine. This broad, anti-inflammatory effect of A_2A receptor activation is a result of the predominant expression of A_2A receptors on monocytes/macrophages, dendritic cells, mast cells, neutrophils, endothelial cells, eosinophils, epithelial cells, as well as lymphocytes, NK cells, and NKT cells. A_2A 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, A_2A receptors participate in tissue remodeling and reparation. Consistent with their multifaceted, immunoregulatory action on immune cells, A_2A 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 A_2A receptors in immune/inflammatory diseases of various organs, including heart, lung, gut, liver, kidney, joints, and brain, as well as the role of A_2A receptors in regulating multiple organ failure and sepsis.

Key Words: macrophage • lymphocyte • neutrophil • cytokine • autoimmune • infection