ASL composition and volume are collectively regulated by epithelial chloride secretion, sodium absorption and secondarily water secretion and absorption [6, 11] . Mounting evidence indicates that paracrine/autocrine purinergic signaling is critical to airway epithelial ion transport and ASL hydration [12] #. Adenosine has been shown to be a potent regulator in the process, which can be directly released by local epithelial cells and immune cells [13] or from extracellular metabolism of ATP [12] #. It is known that ATP is constitutively released by epithelia due to various stimuli including mechanical stretch and shear stress due to respiration [14] . The released ATP is then converted to adenosine by extracellular ectonucleotidases [15] . Thus, ASL has relatively high levels of adenosine. Further studies demonstrate that adenosine largely regulates epithelial CFTR channel function by acting on A 2B AR [16, 17, 18] . Thus, the adenosine-A 2B AR signaling pathway is a crucial element in lung host defense [19, 20] .