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Review
. 2008 Mar 15;44(6):938-55.
doi: 10.1016/j.freeradbiomed.2007.11.016. Epub 2007 Dec 5.

NADPH oxidases in lung biology and pathology: host defense enzymes, and more

Albert van der Vliet  1
Affiliations
Review

NADPH oxidases in lung biology and pathology: host defense enzymes, and more

Albert van der Vliet. Free Radic Biol Med. .

Abstract

The deliberate production of reactive oxygen species (ROS) by phagocyte NADPH oxidase is widely appreciated as a critical component of antimicrobial host defense. Recently, additional homologs of NADPH oxidase (NOX) have been discovered throughout the animal and plant kingdoms, which appear to possess diverse functions in addition to host defense, in cell proliferation, differentiation, and in regulation of gene expression. Several of these NOX homologs are also expressed within the respiratory tract, where they participate in innate host defense as well as in epithelial and inflammatory cell signaling and gene expression, and fibroblast and smooth muscle cell proliferation, in response to bacterial or viral infection and environmental stress. Inappropriate expression or activation of NOX/DUOX during various lung pathologies suggests their specific involvement in respiratory disease. This review summarizes the current state of knowledge regarding the general functional properties of mammalian NOX enzymes, and their specific importance in respiratory tract physiology and pathology.

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Figures

Figure 1
Figure 1
Schematic representation of structural and functional domains of the various classes of mammalian NOX/DUOX proteins and plant respiratory burst oxidase homolog (Rboh) proteins. Modified from (13).
Figure 2
Figure 2
Second messenger production in response to NOX/DUOX activation and association with membrane channels. Activation of NOX/DUOX proteins to produce ROS results in transmembrane electron transfer, causing membrane depolarization and intracellular acidification, leading to activation of e.g. voltage-gated proton channels (VSOP) and Na+/H+ exchange (HNE), which may regulate downstream cellular responses. In addition, intracellular signaling by O2•−/H2O2 may involve their transmembrane transport through aquaporins (AQP) or the chloride channel ClC3.
Figure 3
Figure 3
General oxidative mechanisms involved in the diverse cellular responses to NOX/DUOX activation. Direct oxidant-sensitive targets for NOX/DUOX (including Ca2+ channels and various protein tyrosine phosphatases, PTPs) are indicated in red, and relationships with downstream affected pathways are illustrated.
Figure 4
Figure 4
Schematic illustration of epithelial DUOX activation and its downstream signaling mechanisms, in response to infection and/or injury. P2YR, P2Y receptor; PLC, phospholipase C; IP3, inositol triphosphate; DAG, diacylglycerol; PKC, protein kinase C; EGFR, epidermal growth factor receptor.
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