Date: 12 Apr 2011

Regulation of Airway Nucleotides in Chronic Lung Diseases

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The physiological relevance of the purinergic signaling network for airway defenses is emerging through cumulating reports of abnormal ATP and adenosine (ADO) levels in the airway secretions of patients with asthma, chronic pulmonary obstructive diseases, cystic fibrosis and idiopathic pulmonary fibrosis. The consequences for airway defenses range from abnormal clearance responses to the destruction of lung tissue by excessive inflammation. This chapter reviews the challenges of assessing airway purines in human subjects, and identifies the general trend in aberrant airway composition. Most diseases are associated with an accumulation of ATP and/or ADO in bronchoalveolar lavage, sputum or exhaled breadth condensate. Intriguing is the case of cystic fibrosis patients, which do not accumulate airway ADO, but its precursor, AMP. This observation launched the investigation of ectonucleotidases as target proteins for the correction of airway purine levels in chronic respiratory diseases. This chapter exposes the extensive rearrangement of the enzymatic network taking place in diseased airways, and identifies signaling pathways likely involved in the aberrant regulation of the airway purines.