Alveolar macrophage transcriptomic profiling in COPD shows major lipid metabolism changes
Alveolar macrophage transcriptomic profiling in COPD shows major lipid metabolism changes
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DOI：
10.1183/23120541.00915-2020
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发表时间：
2021-07-01
影响因子：
4.6
通讯作者：
Schultze, Joachim L.
中科院分区：
文献类型：
--
作者：
Fujii, Wataru;Kapellos, Theodore S.;Schultze, Joachim L.
免疫细胞在COPD的发病机制中起主要作用。主要免疫细胞如肺泡巨噬细胞（AM）和嗜中性粒细胞的分布和细胞功能的变化是众所周知的;方法为了确定支气管肺泡灌洗液中主要免疫细胞类型中转录重编程和脂质代谢的变化，我们分析了来自对照组和COPD患者的分选的CD 45 +Lin-HLA-DR+ CD 66 b-自体荧光AM的全转录组和脂质体。我们进一步检测到COPD患者和对照组之间脂质代谢相关基因的显著变化，例如GOLD 2患者的脂肪酸生物合成。基于这些研究结果，在分类AM的202个脂质种类的评估显示胆固醇酯，单酰基甘油和磷脂的变化在疾病等级依赖marty.Conclusions转录组和脂质组分析COPD AM揭示黄金等级依赖性的变化，如胆固醇代谢和干扰素-α和。应答
Background Immune cells play a major role in the pathogenesis of COPD. Changes in the distribution and cellular functions of major immune cells, such as alveolar macrophages (AMs) and neutrophils are well known; however, their transcriptional reprogramming and contribution to the pathophysiology of COPD are still not fully understood.Method To determine changes in transcriptional reprogramming and lipid metabolism in the major immune cell type within bronchoalveolar lavage fluid, we analysed whole transcriptomes and lipidomes of sorted CD45+Lin-HLA-DR+CD66b-Autofluorescencehi AMs from controls and COPD patients.Results We observed global transcriptional reprogramming featuring a spectrum of activation states, including pro- and anti-inflammatory signatures. We further detected significant changes between COPD patients and controls in genes involved in lipid metabolism, such as fatty acid biosynthesis in GOLD2 patients. Based on these findings, assessment of a total of 202 lipid species in sorted AMs revealed changes of cholesteryl esters, monoacylglycerols and phospholipids in a disease grade-dependent manner.Conclusions Transcriptome and lipidome profiling of COPD AMs revealed GOLD grade-dependent changes, such as in cholesterol metabolism and interferon-a and. responses.