Apoptosis in neonatal murine lung exposed to hyperoxia

Exposure to high concentrations of oxygen in the neonatal period may impair lung growth and is a major contributing factor to the development of bronc hopulmonary dysplasia. Cell death from hyperoxic injury may occur through e ither an apoptotic or nonapoptotic pathway, and we were interested in deter mining the type of cell death that occurs in the lung of neonatal mice expo sed to hyperoxia. We found increased levels of Bax messenger RNA, a gene as sociated with apoptosis, in the lungs of neonatal mice born and raised in 9 2% hyperoxia. We next determined the extent of apoptosis taking place in th e lungs of neonatal mice exposed to hyperoxia using terminal deoxyribonucle otidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end label ing in 3.5-, 4.5-, and 5.5-d-old neonatal lung. The number of apoptotic cel ls in peripheral lung was significantly higher in the 3.5-, 4.5-, and 5.5-d -old mice treated with oxygen compared with that in the room-air control mi ce. Further, the number of apoptotic cells in the lung increased with longe r exposure duration. In murine lung bronchus cells exposed to hyperoxia, gr owth arrest occurred after 48 h of oxygen exposure. Using annexin V binding , necrotic cell death was found to be the major form of cell death in these cells after 72 h of hyperoxic exposure. We conclude that 92% hyperoxia cau ses significant lung injury in neonatal mice exposed to hyperoxia, and that the number of apoptotic cells in the lung increases the longer the duratio n of exposure. The increase in apoptosis from hyperoxic exposure during a c ritical period of lung development may be an important factor in the impair ed lung growth and remodeling that occur in animals exposed to high oxygen concentrations. Finally, it appears that hyperoxic injured cells in neonata l lung undergo both apoptotic and nonapoptotic cell death.