期刊
JOURNAL OF LIPID RESEARCH
卷 51, 期 6, 页码 1325-1331出版社
ELSEVIER
DOI: 10.1194/jlr.M001651
关键词
pulmonary alveolar proteinosis; granulocyte-macrophage colony-stimulating factor; peroxisome proliferator-activated receptor-gamma
资金
- North Carolina Biotechnology Center [2005-FRG-1013]
Surfactant accumulates in alveolar macrophages of granulocyte-macrophage colony-stimulating factor (GMCSF) knockout (KO) mice and pulmonary alveolar proteinosis (PAP) patients with a functional loss of GM-CSF resulting from neutralizing anti-GM-CSF antibody. Alveolar macrophages from PAP patients and GM-CSF KO mice are deficient in peroxisome proliferator-activated receptor-gamma (PPAR gamma) and ATP-binding cassette (ABC) lipid transporter ABCG1. Previous studies have demonstrated that GMCSF induces PPAR gamma. We therefore hypothesized that PPAR gamma promotes surfactant catabolism through regulation of ABCG1. To address this hypothesis, macrophage-specific PPAR gamma (MacPPAR gamma) knockout mice were utilized. MacPPAR gamma KO mice develop foamy, lipid-engorged Oil Red O positive alveolar macrophages. Lipid analyses revealed significant increases in the cholesterol and phospholipid contents of MacPPAR gamma KO alveolar macrophages and extracellular bronchoalveolar lavage (BAL)-derived fluids. MacPPAR gamma KO alveolar macrophages showed decreased expression of ABCG1 and a deficiency in ABCG1-mediated cholesterol efflux to HDL. Lipid metabolism may also be regulated by liver X receptor (LXR)-ABCA1 pathways. Interestingly, ABCA1 and LXR beta expression were elevated, indicating that this pathway is not sufficient to prevent surfactant accumulation in alveolar macrophages. These results suggest that PPAR gamma mediates a critical role in surfactant homeostasis through the regulation of ABCG1.-Baker, A. D., A. Malur, B. P. Barna, S. Ghosh, M. S. Kavuru, A. G. Malur, and M. J. Thomassen. Targeted PPAR gamma deficiency in alveolar macrophages disrupts surfactant catabolism. J. Lipid Res. 2010. 51: 1325-1331.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据