Effect of retinol on fetal lamb tracheal epithelium, with and without epidermal growth factor. A model for the effect of retinol on the healing lung of human premature infants.

Twelve pairs of fetal lambs were used to test the hypothesis that the necrotizing tracheobronchitis followed by squamous metaplasia seen in premature infants who develop chronic bronchopulmonary dysplasia might be related to low retinol stores and might, therefore, be reversed by retinol supplementation. Epidermal growth factor (EGF) was used to model the growth factor stimulus initiated by chronic wounding of the airways, and retinol was used as a differentiator of proliferating cells stimulated by EGF. Saline-treated animals were used as controls, as were fetal lambs receiving retinol alone or EGF alone. The effects of EGF on tracheal and bronchial epithelium consisted of proliferation of basal and intermediate cells, necrosis and slough of lining ciliated and mucous-producing cells, followed by squamous metaplasia. In fetal lambs given retinol, plasma, liver and lung retinol levels rose and mucous producing cells were increased in number. In the presence of EGF plus retinol, differentiation of mucous-producing cells was accelerated. We believe that this fetal lamb model with low initial levels of retinol in plasma, liver and lung, treated with EGF may mimic human premature infants with chronic bronchopulmonary dysplasia, and that the addition of retinol in amounts sufficient to raise their tissue levels produces a more normal surface epithelium in conducting airways.