Department of Chemistry, Khalifa University, P.O. Box 127788, Abu Dhabi, United Arab Emirates.
Department of Biomedical Engineering, Khalifa University, P.O. Box 127788, Abu Dhabi, United Arab Emirates.
Lipids Health Dis. 2017 Dec 13;16(1):242. doi: 10.1186/s12944-017-0629-9.
The transformation of normal macrophage cells into lipid-laden foam cells is an important step in the progression of atherosclerosis. One major contributor to foam cell formation in vivo is the intracellular accumulation of cholesterol.
Here, we report the effects of various combinations of low-density lipoprotein, sterols, lipids and other factors on human macrophages, using an automated image analysis program to quantitatively compare single cell properties, such as cell size and lipid content, in different conditions.
We observed that the addition of cholesterol caused an increase in average cell lipid content across a range of conditions. All of the sterol-lipid mixtures examined were capable of inducing increases in average cell lipid content, with variations in the distribution of the response, in cytotoxicity and in how the sterol-lipid combination interacted with other activating factors. For example, cholesterol and lipopolysaccharide acted synergistically to increase cell lipid content while also increasing cell survival compared with the addition of lipopolysaccharide alone. Additionally, ergosterol and cholesteryl hemisuccinate caused similar increases in lipid content but also exhibited considerably greater cytotoxicity than cholesterol.
The use of automated image analysis enables us to assess not only changes in average cell size and content, but also to rapidly and automatically compare population distributions based on simple fluorescence images. Our observations add to increasing understanding of the complex and multifactorial nature of foam-cell formation and provide a novel approach to assessing the heterogeneity of macrophage response to a variety of factors.
正常巨噬细胞向富含脂质的泡沫细胞的转化是动脉粥样硬化进展的重要步骤。体内泡沫细胞形成的一个主要贡献者是胆固醇的细胞内积累。
在这里，我们报告了各种组合的低密度脂蛋白、固醇、脂质和其他因素对人巨噬细胞的影响，使用自动图像分析程序定量比较不同条件下单个细胞的特性，如细胞大小和脂质含量。
我们观察到胆固醇的添加导致在一系列条件下平均细胞脂质含量增加。所有检查的固醇-脂质混合物都能够诱导平均细胞脂质含量增加，反应分布、细胞毒性以及固醇-脂质组合与其他激活因子相互作用的方式存在差异。例如，胆固醇和脂多糖协同作用增加细胞脂质含量，同时与单独添加脂多糖相比增加细胞存活率。此外，麦角固醇和胆固醇半琥珀酸酯引起类似的脂质含量增加，但比胆固醇表现出更大的细胞毒性。
自动图像分析的使用使我们不仅能够评估平均细胞大小和含量的变化，还能够快速自动地根据简单的荧光图像比较群体分布。我们的观察结果增加了对泡沫细胞形成的复杂和多因素性质的理解，并为评估巨噬细胞对各种因素的反应异质性提供了一种新方法。
