重新考察BV2小胶质细胞M1与M2表型的概念,并测试它们对小鼠中风结果的影响

Q4 Medicine Cardiology Plus Pub Date : 2021-10-01 DOI:10.4103/2470-7511.334399
D. Yan, Yongming Zhang, Yu-hua Ji, Tao Wang, Xiao-Xing Xiong, Heng Zhao
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引用次数: 1

摘要

背景:M1和M2是否存在不同的巨噬细胞功能表型一直存在争议。我们通过研究培养的BV2小胶质细胞中M1/M2基因和蛋白质的表达及其对体内卒中结果的影响,对其进行了重新检测。方法:用脂多糖(LPS)和白细胞介素-4(IL-4)对BV2小胶质细胞进行培养和极化,产生M(LPS)表型和M(IL-6)表型,最初分别定义为M1和M2表型。分析了M(LPS)和M(IL-4)表型中典型的M1和M2基因或蛋白质表达模式,并比较了它们对中风结果的独特影响。结果:M(LPS)和M(IL-4)具有明显的形态特征。M(IL-4)具有显著较高的典型M2标记物和其他抗炎基因的基因表达,而M(LPS)具有较高的典型M1标记物和其它促炎基因的基因表现。然而,M(LPS)中M2基因表达也增强,M(IL-4)中M1基因表达增加,尽管水平相对较低。过继转移M(IL-4)可减少梗死并改善神经评分,而M(LPS)巨噬细胞则产生相反的作用。荧光激活细胞分选(FACS)和共聚焦研究表明,M(IL-4)可抑制单核细胞衍生的巨噬细胞和iNOS阳性细胞的浸润,而M(LPS)可促进其浸润。结论:培养的BV2细胞中的M(LPS)和M(IL-4)确实是不同的功能表型,但根据一些典型的基因和蛋白质标记物将其简单地分为M1和M2表型是不准确的。
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Re-visit the concept of M1 versus M2 phenotypes of BV2 microglia and test their effects on stroke outcome in mice
Backgrounds: Whether there are distinctive macrophage functional phenotypes of M1 versus M2 has been debated. We re-examined them by studying M1/M2 gene and protein expressions in cultured BV2 microglial cells and their effects on stroke outcomes in vivo. Methods: BV2 microglia cells were cultured and polarized with lipopolysaccharide (LPS) and interleukin-4 (IL-4) to produce M (LPS) and M (IL-4) phenotypes, which were originally defined as M1 and M2 phenotypes, respectively. Typical M1 and M2 gene or protein expression patterns were analyzed in M (LPS) and M (IL-4) phenotypes and their distinctive effects on stroke outcomes were compared. Results: M (LPS) and M (IL-4) had distinctive morphologies. M (IL-4) had significantly higher gene expressions of the typical M2 markers and other anti-inflammatory genes, while M (LPS) had higher gene expression of typical M1 markers and other pro-inflammatory genes. Nevertheless, M2 gene expressions were also enhanced in M (LPS), and M1 gene expressions were increased in M (IL-4), although with relatively lower levels. Adoptive transfer of M (IL-4) reduced infarction and improved neurological scores, while M (LPS) macrophages generated the opposite effect. Fluorescence activated cell sorting (FACS) and confocal studies suggest that M (IL-4) inhibited, while M (LPS) promoted the infiltration of monocyte-derived macrophages and iNOS-positive cells. Conclusions: M (LPS) and M (IL-4) from cultured BV2 cells indeed are distinctive functional phenotypes, but it is inaccurate to simply classify them into M1 and M2 phenotypes based on a few typical gene and protein markers.
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CiteScore
0.50
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发文量
24
审稿时长
32 weeks
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