Lung surfactant dipalmitoylphosphatidylcholine (DPPC) is endocytosed by alveolar epithelial cells and degraded by lysosomal-type phospholipase A(2) (aiPLA(2)). This enzyme is identical to peroxiredoxin 6 (Prdx6), a bifunctional protein with PLA(2) and GSH peroxidase activities. Lung phospholipid was studied in Prdx6 knockout (Prdx6(-/-)) mice. The normalized content of total phospholipid, phosphatidylcholine (PC), and disaturated phosphatidylcholine (DSPC) in bronchoalveolar lavage fluid, lung lamellar bodies, and lung homogenate was unchanged with age in wildtype mice but increased progressively in Prdx6(-/-) animals. Degradation of internalized [H-3] DPPC in isolated mouse lungs after endotracheal instillation of unilamellar liposomes labeled with [H-3] DPPC was significantly decreased at 2 h in Prdx6(-/-) mice (13.6 +/- 0.3% vs. 26.8 +/- 0.8% in the wild type), reflected by decreased dpm in the lysophosphatidylcholine and the unsaturated PC fractions. Incorporation of [C-14] palmitate into DSPC at 24 h after intravenous injection was decreased by 73% in lamellar bodies and by 54% in alveolar lavage surfactant in Prdx6(-/-) mice, whereas incorporation of [ 3 H] choline was decreased only slightly. Phospholipid metabolism in Prdx6(-/-) lungs was similar to that in wild-type lungs treated with MJ33, an inhibitor of aiPLA(2) activity. These results confirm an important role for Prdx6 in lung surfactant DPPC degradation and synthesis by the reacylation pathway.
