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

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% O-2 until 50% died (LD(50); 7-11 days old). Subsequent litters were exposed to >95% O-2 for 8 days, followed by 60% O-2 until 22-36 days. Controls were exposed to room air. LD(50) 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% O-2, with specific elevations in terminal bronchioles and type II cells at 4 days and the LD(50) 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 LD(50). SP mRNA alterations resolved by 22-36 days. The surfactant system recovers from acute hyperoxic injury, despite continued 60% O-2 exposure.