Role of A2A adenosine receptors in inflammation

A2A adenosine receptors are expressed on immune cells including neutrophils, lymphocytes, eosinophils, monocytes/macrophages, and mast cells. Activation of A2A receptors on these cells stimulates an increase in [cyclic AMP]i and causes a diminution of inflammatory responses. In mast cells, degranulation is inhibited; in neutrophils, adherence is reduced and the release of reactive oxygen species is inhibited; in monocytes, differentiation to macrophages is inhibited and the release of tumor necrosis factor-α is inhibited; and in lymphocytes, TCR-triggered interleukin-2 α chain (CD25) up-regulation is reduced. In vivo, selective adenosine A2A agonists decrease inflammation in both infectious and noninfectious models. High concentrations (micromolar) of the A3 selective agonist, IB-MECA, produce anti-inflammatory responses that are mediated by A2A receptors. Selective activation of A2A adenosine receptors with pharmaceutical agents may be a useful strategy for ameliorating an inappropriate and/or an extensive inflammatory response. Drug Dev. Res. 45:103–112, 1998.