Adenosine and osteopontin contribute to the development of chronic obstructive pulmonary disease

ABSTRACT Chronic obstructive pulmonary disease (COPD) is a major health concern. Adenosine, a signaling molecule generated in response to cell stress, contributes to the pathogenesis of COPD. An established model of adenosine‐mediated lung injury is the adenosine deaminase‐deficient (Ada −/− ) mouse. Os‐teopontin (OPN) is a chemokine that is produced following injury and is implicated in a variety of human pathologies, but its expression and role in the patho‐genesis of COPD have not been examined. To investigate the role of OPN in a model of COPD, Adα −/− double‐knockout mice were generated, and inflammation and air‐space enlargement endpoints were examined. Results demonstrate that Adα _/_ mice exhibit OPN‐dependent neutrophilia, alveolar air‐space enlargement, and increases in mediators of air‐space enlargement. Furthermore, we demonstrate that patients with COPD have increased OPN expression within distal airways in association with clinical airway obstruction. These results suggest that OPN represents a novel biomarker and therapeutic target for patients with COPD.—Schneider, D. J., Lindsay, J. C., Zhou, Y., Molina, J. G., Blackburn, M. R. Adenosine and os‐teopontin contribute to the development of chronic obstructive pulmonary disease. FASEB J . 24, 70–80 (2010). www.fasebj.org