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

TitleAdenosine and osteopontin contribute to the development of chronic obstructive pulmonary disease
Publication TypeJournal Article
Year of Publication2010
AuthorsSchneider DJ, Lindsay JC, Zhou Y, Molina JG, Blackburn MR
JournalFASEB J
Date Published2010 Jan
KeywordsAdenosine, Adenosine Deaminase, Animals, Disease Models, Animal, Emphysema, Female, Gene Expression, Humans, In Vitro Techniques, Macrophages, Alveolar, Mice, Mice, Inbred C57BL, Mice, Knockout, Neutrophils, Osteopontin, Pulmonary Disease, Chronic Obstructive, Pulmonary Fibrosis, Receptor, Adenosine A2B, RNA, Messenger

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. Osteopontin (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 pathogenesis of COPD have not been examined. To investigate the role of OPN in a model of COPD, Ada(-/-) double-knockout mice were generated, and inflammation and air-space enlargement endpoints were examined. Results demonstrate that Ada(-/-) 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.

Alternate JournalFASEB J.
PubMed ID19720619
PubMed Central IDPMC2797041
Grant ListAI-43572 / AI / NIAID NIH HHS / United States
HL-095403 / HL / NHLBI NIH HHS / United States
HL-70952 / HL / NHLBI NIH HHS / United States
TL1 RR 024147 / RR / NCRR NIH HHS / United States