A Role For ATP-signalling In The Pathogenesis Of COPD And Emphysema

Background: Extracellular ATP acts as “danger signal” and can induce inflammation by binding to purinergic receptors (P2R). Chronic obstructive pulmonary disease (COPD) is one of the most common inflammatory diseases of the lung, and pathogenesis is associated with inhalation of cigarette smoke but the underlying mechanisms are incompletely understood. In this work we were interested in the contribution of purinergic receptor signalling to the pathogenesis of COPD. Methods: Lung inflammation and emphysema in mice was induced by exposure to cigarette smoke. The animals were assayed for the features of lung inflammation and emphysema (composition of broncho-alveolar lavage fluid, histology). Results: Exposure to cigarette smoke lead to an increase in BALF ATP levels. This finding was of pathophysiological relevance, as the development of smoke-induced lung inflammation and emphysema was markedly reduced by neutralizing ATP or treatment with P2R antagonists prior to smoke exposure. Furthermore, experiments with P2R-deficient animals revealed that especially the purinergic receptor subtypes P2Y2 and P2X7 contribute to the features of smoke-induced lung inflammation and emphysema. Discussion: In summary we were able to demonstrate that extracellular ATP is involved in the pathogenesis of COPD and emphysema via purinergic receptor signalling. Therefore, targeting purinergic receptors might be a promising approach for the treatment of this devastating disease.