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Am. J. Respir. Cell Mol. Biol., Volume 25, Number 1, July, 2001 51-59

Elevated Expression of Surfactant Proteins in Newborn Rats during Adaptation to Hyperoxia

Carl W. White, Kelly E. Greene, Corrie B. Allen, and John M. Shannon

Departments of Pediatrics and Medicine, National Jewish Medical and Research Center, Denver, Colorado; and Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio

The mechanisms whereby lung adaptation to hyperoxia occurs in the newborn period are incompletely understood. Pulmonary surfactant has been implicated in lung protection against hyperoxic injury, and elevated expression of certain surfactant proteins occurs in lungs of adult rats during adaptation to sublethal oxygen (85% O2). Here we report that newborn rats, which can adapt to even higher levels of hyperoxia (100% O2) than do adult rats, manifest 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 messenger RNAs (mRNAs) for SP-A and SP-B gradually and progressively increased, 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 hyperoxia-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 increased on Day 8. Both SP-A and SP-D proteins were increased in lung lavage samples 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 identical to those of the respective mRNAs. In situ hybridization studies demonstrated 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 pretranslational and post-translational levels in distal lung epithelium during adaptation to hyperoxia in the newborn rat.

Abbreviations: bronchoalveolar lavage, BAL; BAL fluid, BALF; a protein specific for Clara cells, CC-10; complementary DNA, cDNA; messenger RNA, mRNA; phosphate-buffered saline, PBS; surfactant protein, SP; thyroid transcription factor 1, TTF-1.




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