Impaired surfactant phospholipid metabolism in hyperoxic mouse lungs

Abstract

We studied the effect of 98% O2 on the amounts of and in vivo and in vitro synthesis rates of lung phospholipids in the mouse. The alveolar fluid obtained by multiple endobronchial lavages showed a decline in the amounts of all phospholipids between 48 and 72 h. The proportion of phosphatidylcholine that was disaturated did not change up to 96 h. Smaller decreases in phosphatidylcholine of the lung tissue were found at the same times. Between 48 and 72 h the turnover of total and disaturated phosphatidylcholine was greatly decreased, and transit time for both from lung to alveolar fluid was prolonged. At 60 h in vitro incorporation by lung slices of both glycerol and palmitate into disaturated phospholipids was reduced by approximately half, the distribution of label into various phospholipid classes being unchanged. We interpret these data as supporting the hypothesis that hyperoxia impairs the synthesis of surfactant phospholipids in the lung and their transport to the alveolar surface, and that this results in a decrease in the phospholipid content of the alveolar lining layer. These effects could account for altered pulmonary mechanical properties and contribute to the morbidity and mortality of O2 toxicity.