Figure 5.

A, B, Diagrams showing mechanisms of disease in COPD. A, In health, noxious stimuli such as smoking trigger release of mucin granules from airway epithelia into the extracellular space. These granules contain ADP and other nucleotides, which are metabolized on the airway surface to Ado. Ado stimulates AdoRs, which in turn activate CFTR and other channels to promote fluid secretion. The coordinated secretion of mucins and fluid acts to flush noxious stimuli off of the airway surface. B, With progressive disease, mucin secretion is enhanced, but increased extracellular metabolism of Ado from neutrophils or other factors limits its ability to stimulate fluid secretion. The resulting imbalance between mucin and fluid secretion leads to mucus accumulation. Ado = adenosine; AdoR = adenosine receptor; ADP = adenosine diphosphate; CFTR = cystic fibrosis transmembrane conductance regulator; Hyp = hypoxanthine; Xan = xanthine.