Elevated expression of surfactant proteins in newborn rats during adaptation to hyperoxia

The mechanisms whereby lung adaptation to hyperoxia occurs in the newborn p eriod are incompletely understood. Pulmonary surfactant has been implicated in lung protection against hyperoxic injury, and elevated expression of ce rtain surfactant proteins occurs in lungs of adult rats during adaptation t o sublethal oxygen (85% O-2). Here we report that newborn rats, which can a dapt to even higher levels of hyperoxia (100% O-2) than do adult rats, mani fest changes in the lung surfactant proteins (SP), especially SP-A and SP-D . In newborn rats exposed to hyperoxia on Days 3 through 10 of life, lung m essenger RNAs (mRNAs) for SP-A and SP-B gradually and progressively increas ed, relative to levels in age-matched, air-exposed newborns, over this 8-d period. By contrast, SP-C and SP-D mRNAs were maximally increased relative to values in simultaneously air-exposed control rats after 4 d of exposure. Lung mRNA for CC-10, a protein specific for Clara cells, was greater in hy peroxia-exposed rats than in air-exposed control rats on Day 4 of exposure, but not on other days. Lung mRNA for thyroid transcription factor (TTF)-1 was marginally increased on Days 1, 2, 4, and 6, and significantly increase d on Day 8. Both SP-A and SP-D proteins were increased in lung lavage sampl es taken from hyperoxia-exposed newborns, relative to those taken from air- exposed controls, with the greatest increases occurring on Days 6 and 8 of exposure. However, the patterns of increase of the proteins were not identi cal to those of the respective mRNAs. in situ hybridization studies demonst rated increases in SP-D, and to a lesser extent in SP-A, in peripheral lung tissues from oxygen-exposed newborns. Taken together, these data indicate that specific surfactant proteins are upregulated at both the pretranslatio nal and post-translational levels in distal lung epithelium during adaptati on to hyperoxia in the newborn rat.