title: Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense.
abstract: Lactoperoxidase (LPO) is an enzyme with antimicrobial properties present in saliva, milk, tears, and airway secretions. Although the formation of microbicidal oxidants by LPO has been recognized for some time, the source of hydrogen peroxide (H2O2) for LPO-catalyzed reactions remains unknown. Reactive oxygen species produced by the phagocyte NADPH oxidase (phox) play a critical role in host defense against pathogens; however, analogous oxidant-generating systems in other tissues have not been associated with antimicrobial activity. Several homologues of gp91phox, the catalytic core of this enzyme, were described recently; dual oxidase (Duox)1/thyroid oxidase 1 and Duox2/thyroid oxidase 2 were identified in the thyroid gland and characterized as H2O2 donors for thyroxin biosynthesis. We examined Duox1 and Duox2 expression in secretory glands and on mucosal surfaces and give evidence for their presence and activity in salivary glands, rectum, trachea, and bronchium. Epithelial cells in salivary excretory ducts and rectal glands express Duox2, whereas tracheal and bronchial epithelial cells express Duox1. Furthermore, we detected Duox1-dependent H2O2 release by cultured human bronchial epithelial cells. Our observations suggest that Duox1 and Duox2 are novel H2O2 sources that can support LPO-mediated antimicrobial defense mechanisms on mucosal surfaces.
authors.affiliation: Department of Physiology, Semmelweis University, Faculty of Medicine, Bethesda, Maryland, USA.
authors.forename: Miklós
authors.initials: M
authors.lastname: Geiszt
authors.forename: Jassir
authors.initials: J
authors.lastname: Witta
authors.forename: Judit
authors.initials: J
authors.lastname: Baffi
authors.forename: Kristen
authors.initials: K
authors.lastname: Lekstrom
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Leto
mesh_terms: D001980:Bronchi / Q000033:anatomy & histology; D000074623:Dual Oxidases; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism; D005420:Flavoproteins; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D018928:Immunity, Mucosal; D007784:Lactoperoxidase / Q000032:analysis / Q000378:metabolism; D008954:Models, Biological; D009092:Mucous Membrane / Q000737:chemistry / Q000378:metabolism*; D019255:NADPH Oxidases / Q000032:analysis / Q000378:metabolism; D010088:Oxidoreductases / Q000032:analysis / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D012007:Rectum / Q000737:chemistry; D020545:Respiratory Mucosa / Q000378:metabolism; D012137:Respiratory System / Q000033:anatomy & histology; D018987:Salivary Ducts / Q000737:chemistry; D012469:Salivary Glands / Q000033:anatomy & histology / Q000378:metabolism; D027981:Symporters / Q000032:analysis / Q000378:metabolism; D000099209:Sodium-Iodide Symporters
chemical_list: D000074623:Dual Oxidases; D005420:Flavoproteins; D006861:Hydrogen Peroxide; D007784:Lactoperoxidase; D019255:NADPH Oxidases; D010088:Oxidoreductases; D012333:RNA, Messenger; D027981:Symporters; D000099209:Sodium-Iodide Symporters; C431513:DUOX1 protein, human