AJP - Lung Cellular and Molecular Physiology, Vol 272, Issue 4 720-L730, Copyright © 1997 by American Physiological Society

ARTICLES

Changes in surfactant protein gene expression in a neonatal rabbit model of hyperoxia-induced fibrosis

C. T. D'Angio, J. N. Finkelstein, M. B. Lomonaco, A. Paxhia, S. A. Wright, R. B. Baggs, R. H. Notter and R. M. Ryan
Department of Pediatrics (Neonatology), Strong Children's Research Center, University of Rochester, New York 14642, USA.

Lung injuries, including bronchopulmonary dysplasia, alter the surfactant system. We developed a newborn rabbit model of acute, followed by chronic, hyperoxic injury to study surfactant protein (SP) gene expression. Initial litters were exposed to >95% O2 until 50% died (LD50; 7-11 days old). Subsequent litters were exposed to >95% O2 for 8 days, followed by 60% O2 until 22-36 days. Controls were exposed to room air. LD50 animals displayed acute pulmonary inflammation, edema, protein leak, and surfactant dysfunction. These changes resolved, and fibrosis developed by 22 days. Whole lung SP-A mRNA expression (measured by membrane hybridization) was twice control levels at 4 days of >95% O2, with specific elevations in terminal bronchioles and type II cells at 4 days and the LD50 by in situ hybridization. Whole lung SP-B and SP-C mRNA were unchanged from control throughout exposure. However, in situ hybridization showed elevations in SP-B and SP-C mRNA in type II cells in inflamed areas at the LD50. SP mRNA alterations resolved by 22-36 days. The surfactant system recovers from acute hyperoxic injury, despite continued 60% O2 exposure.

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