Adenosine deaminase-deficient mice as models for adenosine-mediated lung inflammation and damage

Adenosine has been implicated to play a role in the inflammatory lung disease, asthma; however, there are few in vivo model systems with which to study the role of adenosine in aspects of this disease. We recently generated mice deficient in the purine catabolic enzyme adenosine deaminase (ADA) that controls the levels of adenosine in tissues and cells. Results presented here demonstrate that elevated adenosine levels in ADA-deficient mice result in abnormal lung development and the promotion of lung inflammation and damage. ADA-deficient mice exhibit alveolar defects that are overcome by biochemically restoring ADA enzymatic activity to these animals. In addition, lowering ADA substrates in the lung using enzyme therapy reverses lung eosinophilia and mucus production. These results suggest that elevated adenosine, and perhaps abnormal adenosine signaling, are implicated in abnormal lung development and lung inflammation and damage in ADA-deficient mice. These mice will therefore serve as useful in vivo models in which to study the role of purinergic signaling in aspects of lung development and disease. Drug Dev. Res. 52:416-423, 2001. (C) 2001 Wiley-Liss, Inc.