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BackgroundCOPD is an inflammatory disease usually associated with cigarette smoking (CS) with an increasing global prevalence and no effective medication. Extracellular ATP is increased in the COPD affected lung and may play a key role in driving CS-induced airway inflammation, but the mechanism involved in ATP release has eluded researchers. Recently, the transient receptor potential (TRP) and pannexin-1 channels have been suggested to play a role in other experimental paradigms. Thus, the aim of this work is to investigate if these channels are involved in CS-induced ATP release in the lung.MethodsPrimary human cells were exposed to CS and extracellular ATP levels measured. Mice were exposed to mainstream CS and airway inflammation assessed. TRPV1/4 mRNA expression was assessed in human lung parenchyma.ResultsCS exposure caused a dose-related increase in ATP from primary airway bronchial epithelial cells. This was attenuated by blockers of TRPV1, TRPV4 and pannexin-1 channels. Parallel data was obtained using murine acute CS-driven model systems. Finally, TRPV1/4 mRNA expression was increased in lung tissue samples from patients with COPD.ConclusionsExtracellular ATP is increased in the COPD affected lung and may play a key role in driving disease pathophysiology. These experiments uncover a novel mechanism which may be responsible for CS-induced ATP release. These findings highlight novel targets that could lead to the development of medicine to treat this devastating disease.

Original publication




Journal article



Publication Date





1080 - 1089


Respiratory Pharmacology, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, UK.


Lung, Bronchi, Respiratory Mucosa, Neutrophils, Cells, Cultured, Animals, Mice, Inbred C57BL, Mice, Knockout, Humans, Pulmonary Disease, Chronic Obstructive, Connexins, Nerve Tissue Proteins, RNA, Messenger, Adenosine Triphosphate, Smoking, Tobacco Smoke Pollution, Gene Expression Regulation, Adult, Aged, Middle Aged, Female, Male, TRPV Cation Channels, Interleukin-1beta, Young Adult, Receptors, Purinergic P2X7