title: Altered lung phospholipid metabolism in mice with targeted deletion of lysosomal-type phospholipase A2.
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.
authors.affiliation: Institute for Environmental Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA. abf@mail.med.upenn.edu
authors.forename: Aron B
authors.initials: AB
authors.lastname: Fisher
authors.forename: Chandra
authors.initials: C
authors.lastname: Dodia
authors.forename: Sheldon I
authors.initials: SI
authors.lastname: Feinstein
authors.forename: Ye-Shih
authors.initials: YS
authors.lastname: Ho
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002118:Calcium / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology; D017353:Gene Deletion; D005979:Glutathione Peroxidase / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010477:Perfusion; D010544:Peroxidases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; D010641:Phenotype; D010713:Phosphatidylcholines / Q000378:metabolism; D010741:Phospholipases A / Q000235:genetics* / Q000502:physiology*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism; D013501:Surface-Active Agents / Q000378:metabolism; D013997:Time Factors
chemical_list: D008081:Liposomes; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; D010743:Phospholipids; D013501:Surface-Active Agents; D015060:1,2-Dipalmitoylphosphatidylcholine; D010544:Peroxidases; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; C515983:Prdx6 protein, mouse; D005979:Glutathione Peroxidase; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium