ATP and the pathogenesis of COPD.
Extracellular ATP is a signalling molecule that often serves as a danger signal to alert the immune system of tissue damage. This molecule activates P2 nucleotide receptors, that include the ionotropic P2X receptors and the metabotropic P2Y receptors. Several publications highlight the importance of purinergic signalling in the pathogenesis of chronic airway inflammation. Recently, it has been reported that ATP accumulates in the airways of both animal models and patients with asthma or chronic obstructive pulmonary diseases (COPD); however, the role and function of ATP in the diseases process of COPD are not well understood. In this perspective, a brief overview is given on the role of ATP and P2 receptors in the pathogenesis of lung emphysema and COPD with a focus on neutrophils as messengers in intercellular communication between epithelial cells and macrophages and the activation of inflammasome pathways. Finding the link between purinergic signalling with inflammasome pathways will be a challenge for the future and could lead to the discovery of new therapeutic drugs for suppressing inflammation in the lungs of COPD patients.
Mortaz
Esmaeil
E
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, P.O. Box 80.082, 3508 TB Utrecht, The Netherlands. e.mortaz@uu.nl
Folkerts
Gert
G
Nijkamp
Frans P
FP
Henricks
Paul A J
PA
D000255:Adenosine Triphosphate / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008954:Models, Biological; D009504:Neutrophils / Q000276:immunology; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*
D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate