A2B Adenosine Receptors Regulate the Mucus Clearance Component of the Lung's Innate Defense System

Adenosine (ADO) signaling is altered in both asthma and chronic obstructive pulmonary disease, and the A2B adenosine receptor (A2B-R) may drive pulmonary inflammation. Accordingly, it has been proposed that specific inhibition of the A2B-R could treat inflammatory lung diseases. However, stimulation of the cystic fibrosis transmembrane conductance regulator (CFTR) by ADO may be crucial in permitting the superficial epithelium to maintain airway surface liquid (ASL) volume, which is required to ensure hydrated and clearable mucus. Our goal was to determine which ADO receptor (ADO-R) underlies ASL volume regulation in bronchial epithelia. We used PCR techniques to determine ADO-R expression in bronchial epithelia and used nasal potential difference measurements, Ussing chambers studies, and XZ-confocal microscopy to look at Cl- secretion and ASL volume regulation. The A2B-R was the most highly expressed ADO-R in donor specimens of human bronchial epithelia, and inhibition of ADO-R in vivo prevented activati...