Altered lung phospholipid metabolism in mice with targeted deletion of lysosomal-type phospholipase A21

Abstract

Lung surfactant dipalmitoylphosphatidylcholine (DPPC) is endocytosed by alveolar epithelial cells and degraded by lysosomal-type phospholipase A2 (aiPLA2). This enzyme is identical to peroxiredoxin 6 (Prdx6), a bifunctional protein with PLA2 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 wild-type mice but increased progressively in Prdx6−/− animals. Degradation of internalized [3H]DPPC in isolated mouse lungs after endotracheal instillation of unilamellar liposomes labeled with [3H]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 [14C]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 [3H]choline was decreased only slightly. Phospholipid metabolism in Prdx6−/− lungs was similar to that in wild-type lungs treated with MJ33, an inhibitor of aiPLA2 activity.These results confirm an important role for Prdx6 in lung surfactant DPPC degradation and synthesis by the reacylation pathway.

Keywords

• peroxiredoxin 6
• lung surfactant
• dipalmitoylphosphatidylcholine
• phospholipid remodeling
• phospholipid synthesis