Purinergic P2X7 receptor: a pivotal role in inflammation and immunomodulation

Many, potentially all, inflammatory and immune cells express purinergic receptors of the P1 and P2 type. In recent years, availability of molecular probes and, in some cases, specific antibodies has initiated an investigation of their possible involvement in the inflammatory response. A very recent acquisition is that, besides expressing purinergic receptors, immune cells also secrete ATP, that, once in the extracellular milieu, undergoes hydrolysis by various hydrolases or kinases. Besides active secretion, ATP can also leak into the pericellular space as a consequence of cell damage. Although adenosine appears to have a preeminent anti-inflammatory activity, ATP by means of the P2X7 receptor seems to act as a proinflammatory mediator, a cytotoxic factor, or both. The combined activity of adenosine and ATP provides means for a fine modulation of the inflammatory response, depending on the amount of extracellular ATP, the rate of hydrolysis and the level of expression of P2 and P1 receptors. The P2X7 receptor appears to be involved in several processes relevant to inflammation (interleukin-1b release, cytotoxicity, formation of macrophage polykarions), thus, it may be an appealing target for pharmacologic intervention. Drug Dev. Res. 45:207– 213, 1998.