Oxidant-mediated ciliary dysfunction in human respiratory epithelium.
Exposure of human nasal ciliated epithelium to reactive oxidants generated by the enzymatic xanthine-xanthine oxidase superoxide/hydrogen peroxide (H2O2) and glucose-glucose oxidase H2O2-generating systems, or to reagent H2O2 or hypochlorous acid (HOCl) resulted in significant alterations in ciliary beating. The earliest change noted was the presence of ciliary slowing, progressing eventually to complete ciliary stasis in some areas. Ciliary dyskinesia was seen within the first hour, often from as early as 15 min after exposure of the cells to reactive oxidants. Using peroxidases, various antioxidant enzymes, and oxidant scavengers, we confirmed that these detrimental effects on ciliary function were mediated primarily by H2O2 and HOCl. Moreover, 3-aminobenzamide (3-ABA), an inhibitor of the DNA repair enzyme poly ADP ribose polymerase, prevented H2O2-mediated inhibition of ciliary function, indicating that oxidant-mediated damage to DNA may well be the basis of the effects of H2O2 on ciliated epithelium. Acute and chronic inflammatory responses may therefore present the possible threat of H2O2- or HOCl-inflicted injury on bystander respiratory epithelium, leading to ciliary dyskinesia and slowing.
Department of Medicine, Hillbrow Hospital, Johannesburg, South Africa.
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C
Feldman
R
R
Anderson
K
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Kanthakumar
A
A
Vargas
P J
PJ
Cole
R
R
Wilson
D002374:Catalase / Q000494:pharmacology; D002923:Cilia / Q000187:drug effects / Q000502:physiology*; D005949:Glucose Oxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D009297:Nasal Mucosa / Q000502:physiology*; D016877:Oxidants / Q000494:pharmacology*; D012973:Sodium Hypochlorite / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D019820:Xanthine; D014969:Xanthine Oxidase / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism
D016877:Oxidants; D014970:Xanthines; D013481:Superoxides; D019820:Xanthine; D006861:Hydrogen Peroxide; D012973:Sodium Hypochlorite; D005949:Glucose Oxidase; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase