Oxidant-mediated ciliary dysfunction in human respiratory epithelium

Abstract

Exposure of human nasal ciliated epithelium to reactive oxidants generated by the enzymatic xanthine-xanthine oxidase superoxide/hydrogen peroxide (H₂O₂) and glucose-glucose oxidase H_2OO₂-generating systems, or to reagent H₂O₂ or hypochlorous acid (HOCl) resulted in significant alterations in ciliary beating. The earlist 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 after exposure of the cells to reactive oxidants. Using peroxidases, various antioxidant enzymes, and oxidant scavengers, we confirmed that these detrimental effect on ciliary function were mediated primarily by H₂O₂ and HOCl. Moreover, 3-aminobenzamide (3-ABA), an inhibitor of the DNA repair enzyme 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.