Toxic Effects of Oxygen on Cultured Human Neonatal Respiratory Epithelium

Abstract

Extract: Explants of tracheal epithelium from each of six human neonates were exposed to both 80% and 20% oxygen under otherwise identical culture conditions. Cessation of ciliary movement and carbon particle transport occurred after 48–96 hr of exposure to 80% oxygen, but not after 168 hr of exposure to 20% oxygen.

This alteration of ciliary function was related temporally to squamous metaplasia, or to degeneration and sloughing of cells from the surface epithelium. Explants secreted more mucin and lysozyme during the first 24–72 hr of culture in 80% oxygen. Thereafter, diminished secretion was observed, apparently related to loss of goblet cells from the surface epithelium and failure to discharge the secretory products of submucosal glands. These findings indicate that high oxygen concentrations at atmospheric pressure alone can cause marked alterations of structure and function in neonatal large airways epithelium. Onset of these changes corresponds to the time when the earliest clinical and cytologic evidence of bronchopulmonary dysplasia has been detected, suggests that similar oxygen-induced changes are produced in vivo. Loss of mucociliary function may be an important pathogenetic component of bronchopulmonary dysplasia.

Speculation: Organ culture of human large airways epithelium appears to be a useful model for study of pulmonary oxygen toxicity. Studies of oxygen concentrations and duration of exposure tolerated by human respiratory epithelium, the cellular mechanisms of oxygen-induced alteration, and the use of pharmacologic agents to prevent or delay onset of toxic changes may be facilitated by using this in vitro technique.

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