Department of Medicine, Keck School of Medicine, Gastroenterology & Hepatology, Research Center for Liver Disease, University of Southern California (USC), Los Angeles, CA, United States.
Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, United States.
Front Immunol. 2021 May 3;12:671073. doi: 10.3389/fimmu.2021.671073. eCollection 2021.
The liver is the central organ for cholesterol synthesis and homeostasis. The effects of dietary cholesterol on hepatic injury, mainly of oxidized low-density lipoproteins (OxLDL), are not fully understood. Here, we show that the degree of cholesterol oxidation had different impacts on the global gene expression of human M2-like macrophages, with highly oxidized LDL causing the most dramatic changes. M2-like macrophages and Kupffer cells undergo M4-like polarization, decreasing the expression of important markers, such as IL10, MRC1, and CD163. These cells also displayed functional changes, with reduced phagocytic capacity, increased neutrophil recruitment, and more effective neutrophil extracellular traps (NETs) induction. Our findings provide a link between LDL oxidation and modification of peripheral and liver macrophage function.
肝脏是胆固醇合成和稳态的中心器官。饮食胆固醇对肝损伤的影响，主要是氧化型低密度脂蛋白（OxLDL），尚未完全阐明。在这里，我们表明胆固醇氧化的程度对人 M2 样巨噬细胞的整体基因表达有不同的影响，高度氧化的 LDL 引起的变化最大。M2 样巨噬细胞和枯否细胞发生 M4 样极化，减少了重要标志物如 IL10、MRC1 和 CD163 的表达。这些细胞还表现出功能变化，吞噬能力降低，中性粒细胞募集增加，以及更有效的中性粒细胞胞外诱捕网（NETs）诱导。我们的研究结果提供了 LDL 氧化与外周和肝脏巨噬细胞功能改变之间的联系。
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