[Frontiers in Bioscience S3, 1443-1456, June 1, 2011]

P2 receptors and extracellular ATP: a novel homeostatic pathway in inflammation

Martijn Jan Leo Bours1, Pieter Cornelis Dagnelie1, Anna Lisa Giuliani2,3, Anke Wesselius1, Francesco Di Virgilio2,3

1Maastricht University, School for Public Health and Primary Care (CAPHRI), P.O. Box 616, 6200 MD Maastricht, The Netherlands, 2 University of Ferrara, Department of Experimental and Diagnostic Medicine, Section of General Pathology, and 3Interdisciplinary Center for the Study in Inflammation, Via Borsari 46, I-44100 Ferrara, Italy


1. Abstract
2. Introduction
3. Is extracellular ATP present at inflammatory foci?
4. Does reduced extracellular ATP affect inflammation?
5. Does P2 receptor stimulation influence inflammation?
6. Do P2 receptors play a role in "osteoimmunology"?
7. Conclusion and therapeutical perspectives
8. Acknowledgement
9. References


Inflammation is an important homeostatic response, which is managed by a complex network of interrelated pathways that determine the level, intensity and localization of inflammation. We now know that purinergic signalling is one of the pathways influencing the initiation, progression and down-modulation of the inflammatory response. Here, we review recent evidence on the role in inflammation of the purinergic signalling system, which is comprised of extracellular ATP, P2 receptors and ecto-enzyme cascades. Recent animal studies with a newly developed bioluminescent ATP probe (pmeLUC), enabling measurement of pericellular ATP in situ, have provided proof that ATP is present in inflamed tissues in vivo at extracellular concentrations sufficient for P2 receptor activation. Increased extracellular ATP levels amplify inflammation in vivo by promoting leukocyte recruitment and NALP3-inflammasome activation via P2X7. Lowering extracellular ATP levels in inflamed tissues, for instance by stimulating its breakdown, inhibits the inflammatory response in vivo. In view of its important role in inflammation, the purinergic signalling system is bound to yield novel therapeutic opportunities for the treatment of inflammatory diseases.