Zinc metabolism in the airway: basic mechanisms and drug targets

Zinc, an essential dietary metal, has special roles in the conducting airways. Under the control of specific zinc transporters, abundant labile zinc localizes to the apical cytoplasm of airway epithelium. Zinc influences a number of important airway proteins, including ADAM33 metalloproteinase, beta(2) adrenoreceptors and nuclear factor-kappa B, and has anti-inflammatory, anti-oxidant and pro-survival actions. Zinc deficiency results in enhanced oxidative damage in the airways by causing infiltration of inflammatory cells and increased superoxide and nitric oxide production. When zinc deficiency occurs in conjunction with acute lung injury or asthma, a more intense inflammation is produced. Zinc is also able to restore chloride secretion in cystic fibrosis models. Research priorities include the development of safe and non-invasive ways to monitor airway zinc levels and to supplement airway zinc when needed.