%0 Journal Article %A Zsofia Lazar %A Nina Müllner %A Monica Lucattelli %A Cemil Korcan Ayata %A Sanja Cicko %A Gennady G. Yegutkin %A Giovanna De Cunto %A Tobias Müller %A Anja Meyer %A Madelon Hossfeld %A Stephan Sorichter %A Ildiko Horvath %A Christian J. Virchow %A Simon C. Robson %A Giuseppe Lungarella %A Marco Idzko %T NTPDase1/CD39 and aberrant purinergic signalling in the pathogenesis of COPD %D 2016 %R 10.1183/13993003.02144-2014 %J European Respiratory Journal %P 254-263 %V 47 %N 1 %X Purinergic receptor activation via extracellular ATP is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Nucleoside triphosphate diphosphohydrolase-1/CD39 hydrolyses extracellular ATP and modulates P2 receptor signalling.We aimed to investigate the expression and function of CD39 in the pathogenesis of cigarette smoke-induced lung inflammation in patients and preclinical mouse models. CD39 expression and soluble ATPase activity were quantified in sputum and bronchoalveolar lavage fluid (BALF) cells in nonsmokers, smokers and COPD patients or mice with cigarette smoke-induced lung inflammation. In mice, pulmonary ATP and cytokine concentrations, inflammation and emphysema were analysed in the presence or absence of CD39.Following acute cigarette smoke exposure CD39 was upregulated in BALF cells in smokers with further increases in COPD patients. Acute cigarette smoke exposure induced CD39 upregulation in murine lungs and BALF cells, and ATP degradation was accelerated in airway fluids. CD39 inhibition and deficiency led to augmented lung inflammation; treatment with ATPase during cigarette smoke exposure prevented emphysema.Pulmonary CD39 expression and activity are increased in COPD. CD39 deficiency leads to enhanced emphysema in mice, while external administration of a functional CD39 analogue partially rescues the phenotype. The compensatory upregulation of pulmonary CD39 might serve as a protective mechanism in cigarette smoke-induced lung damage.The upregulation of pulmonary ATPase is a protective mechanism in cigarette smoke-induced lung inflammation http://ow.ly/S5YcC %U https://erj.ersjournals.com/content/erj/47/1/254.full.pdf