Conversion of human M-CSF macrophages into foam cells reduces their proinflammatory responses to classical M1-polarizing activation
Conversion of human M-CSF macrophages into foam cells reduces their proinflammatory responses to classical M1-polarizing activation
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DOI：
10.1016/j.atherosclerosis.2016.03.012
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发表时间：
2016-05-01
期刊：
影响因子：
5.3
通讯作者：
Kovanen, Petri T.
中科院分区：
文献类型：
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作者：
da Silva, Rafaela F.;Lappalainen, Jani;Kovanen, Petri T.
背景：在动脉粥样硬化病变中，富含胆固醇的巨噬细胞泡沫细胞形成并暴露于m1和m2极化因子。然而，极化因子对泡沫细胞的促炎和抗炎潜能的影响尚不清楚。目的：探讨m1和m2极化因子对培养的人巨噬细胞泡沫细胞促炎基因和抗炎基因表达的影响。方法与结果：人单核细胞在M-CSF作用下分化为巨噬细胞，再经乙酰化LDL培养转化为载胆固醇泡沫细胞。生成的巨噬细胞和泡沫细胞通过LPS和ifn - γ的经典激活被极化为M1表型，或者通过IL-4的替代激活被极化为M2表型。当受到m1极化因子的影响时，巨噬细胞对几个关键的促炎基因（TNFA、IL1B、CXCL8、CCL19和COX2）的典型上调做出反应，而抗炎基因（MRC1、CCL17和IL10）则表现出不同的反应。泡沫细胞再次对m1极化因子表现出较弱的反应，这表明促炎基因上调减少，tnf - α分泌减少，nf - κ B活性降低。当受到可选的M2极化时，巨噬细胞和泡沫细胞都以典型的抗炎基因上调做出反应，这在两种细胞类型中都是相同的幅度。结论：将培养的人巨噬细胞转化为泡沫细胞可抑制其对m1极化因子的促炎反应。因此，在动脉粥样硬化病变的m1极化微环境中，泡沫细胞的形成可能局部削弱动脉粥样硬化中巨噬细胞依赖的炎症成分。2016爱思唯尔爱尔兰有限公司版权所有。
Background: In atherosclerotic lesions, cholesterol-laden macrophage foam cells are formed and exposed to M1-and M2-polarizing factors. However, the effects of the polarizing factors on the proinflammatory and the anti-inflammatory potential of foam cells are not known.Objective: To investigate the effects of M1-and M2-polarizing factors on the expression of pro-and anti-inflammatory genes in cultured human macrophage foam cells.Methods and Results: Human monocytes were differentiated into macrophages in the presence of M-CSF, and then converted into cholesterol-loaded foam cells by incubation with acetylated LDL. The generated macrophages and foam cells were polarized into the M1 phenotype by classical activation with LPS and IFN-gamma, or into the M2 phenotype by alternative activation with IL-4. When subjected to the M1-polarizing factors, the macrophages responded by typical upregulation of several key proinflammatory genes (TNFA, IL1B, CXCL8, CCL19, and COX2), while the anti-inflammatory genes (MRC1, CCL17, and IL10) displayed variable responses. The foam cells, again, showed a weaker response to the M1-polarizing factors, as indicated by reduced upregulation of the proinflammatory genes, reduced secretion of TNF-alpha, and a trend towards lower NF-kappa B activity. When subjected to alternative M2 polarization, both macrophages and foam cells responded by a typical upregulation of the anti-inflammatory genes, which was of equal magnitude in both cell types.Conclusions: Conversion of cultured human macrophages into foam cells suppresses their proinflammatory responses to M1-polarizing factors. Thus, in M1-polarizing microenvironments of atherosclerotic lesions, foam cell formation may locally weaken the macrophage-dependent inflammatory component of atherogenesis. (C) 2016 Elsevier Ireland Ltd. All rights reserved.