Hyperoxia impairs postnatal alveolar epithelial development via NADPH oxidase in newborn mice

Hyperoxia disrupts postnatal lung development in part through induc-ing inflammation. To determine the contribution of leukocyte-derived reactive oxygen species, we exposed newborn wild-type and NADPH oxidase p47phox subunit null (p47phox/) mice to air or acute hyper-oxia (95 % O2) for up to 11 days. Hyperoxia-induced pulmonary neutrophil influx was similar in wild-type and p47/ mice at post-natal days (P) 7 and 11. Macrophages were decreased in wild-type hyperoxia-exposed mice compared with p47phox/ mice at P11. Hyperoxia impaired type II alveolar epithelial cell and bronchiolar epithelial cell proliferation, but depression of type II cell proliferation was significantly less in p47/ mice at P3 and P7, when inflamma-tion was minimal. We found reciprocal results for the expression of the cell cycle inhibitor p21cip/waf in type II cells, which was induced in 95 % O2-exposed wild-type mice, but significantly less in p47phox/ littermates at P7. Despite partial preservation of type I