Apoptosis is an immunologically silent process, but the mechanisms underlying this have yet to be fully defined. In eLife, Nagata and colleagues find an important role for adenosine monophosphate (AMP) in mediating the anti-inflammatory effects of apoptotic cells on macrophages. Caspases triggered during the induction of apoptosis cleave and activate the plasma membrane channel pannexin-1, which allows its release of AMP. This is then converted extracellularly to adenosine, possibly through the action of the ectonuclease CD73 expressed on macrophages. The adenosine then triggers the macrophage purinergic receptor A2a to elicit an anti-inflammatory program characterized by the expression of thrombospondin and the Nr4a family of nuclear receptors. Accordingly, administration of AMP in vivo lessens inflammation in a zymosan-induced model of peritonitis and in a pannexin-1- and A2a-dependent manner. Therefore, AMP release is another mechanism by which apoptotic cells are able to 'calm' macrophages.

eLife (25 March 2014) doi:10.7554/eLife.02172