Mechanisms and Function of DUOX in Epithelia of the Lung

Abstract

The human lung produces considerable amounts of H₂O₂. In the normal uninflamed epithelium of both the airways and the alveoli, mucosal release of H₂O₂ is readily detected both in cell cultures in vitro and in the exhaled breath of humans. The dual oxidases DUOX1 and DUOX2 are the H₂O₂-producing isoforms of the NADPH oxidase family found in epithelial cells. The DUOXs are prominently expressed at the apical cell pole of ciliated cells in the airways and in type II cells of the alveoli. Recent studies focused on the functional consequences of H₂O₂ release by DUOX into the lung lining fluid. In the airways, a major function of DUOX is to support lactoperoxidase (LPO) to generate bactericidal OSCN⁻, and there are indications that the DUOX/LPO defense system is critically dependent on the function of the CFTR Cl⁻ channel, which provides both SCN⁻ (for LPO function) and HCO₃ ⁻ (for pH adjustment) to the airway surface liquid. Although DUOX is also functional in the alveolar epithelium, no comparable heme peroxidase is present in the alveolus, and thus DUOX-mediated H₂O₂ release by alveolar cells may have other functions, such as cellular signaling. Antioxid. Redox Signal. 11, 2453–2465.