Lysosomal acid lipase over-expression disrupts lamellar body genesis and alveolar structure in the lung.
Lysosomal acid lipase over-expression disrupts lamellar body genesis and alveolar structure in the lung.
复制标题
溶酶体酸性脂肪酶过度表达会破坏肺中的层状体发生和肺泡结构。
DOI：
10.1111/j.1365-2613.2007.00547.x
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发表时间：
2007
影响因子：
3
通讯作者：
Du,Hong
中科院分区：
文献类型：
--
作者：
Li,Yuan;Qin,Yulin;Li,Huimin;Wu,Renliang;Yan,Cong;Du,Hong
中性脂在肺中的功能作用还知之甚少。溶酶体酸性脂肪酶(Lal)是胆固醇酯和甘油三酯在溶酶体中分解生成游离脂肪酸和胆固醇的关键酶。人LAL在小鼠呼吸道上皮细胞的多西环素控制系统中过表达，以加速细胞内中性脂肪降解并扰乱肺内表面活性物质的动态平衡。在该动物模型中，肺泡灌洗液(BALF)中肺表面活性物质的中性脂质浓度降低，同时肺表面活性蛋白C(SP-C)基因表达降低。肺泡II型上皮细胞(AT II细胞)板层小体的大小和数量明显减少。BALF中表面活性物质循环所需的巨噬细胞数量也显著减少。作为这些综合作用的结果，观察到肺泡结构的肺气肿。综上所述，中性脂平衡对于维持板层小体发生和肺泡结构是必不可少的。
The functional role of neutral lipids in the lung is poorly understood. Lysosomal acid lipase (LAL) is a critical enzyme in hydrolysis of cholesteryl esters and triglycerides to generate free fatty acids and cholesterol in lysosomes. Human LAL was over‐expressed in a doxycycline‐controlled system in mouse respiratory epithelial cells to accelerate intracellular neutral lipid degradation and perturb the surfactant homeostasis in the lung. In this animal system, neutral lipid concentrations of pulmonary surfactant were reduced in bronchoalveolar lavage fluid (BALF) in association with decrease of surfactant protein C (SP‐C) gene expression. The size and the number of lamellar bodies in alveolar type II epithelial cells (AT II cells) were significantly reduced accordingly. The number of macrophages required for surfactant recycling in BALF was also significantly reduced. As a result of these combinatory effects, emphysema of the alveolar structure was observed. Taken together, neutral lipid homeostasis is essential for maintenance of lamellar body genesis and the alveolar structure in the lung.