Novel Markers to Delineate Murine M1 and M2 Macrophages.
Novel Markers to Delineate Murine M1 and M2 Macrophages.
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DOI：
10.1371/journal.pone.0145342
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Guerau-de-Arellano M
中科院分区：
文献类型：
--
作者：
Jablonski KA;Amici SA;Webb LM;Ruiz-Rosado Jde D;Popovich PG;Partida-Sanchez S;Guerau-de-Arellano M
经典激活（M1）和替代激活（M2）的巨噬细胞呈现出不同的表型和功能。在体内，巨噬细胞表型呈现出一个谱系，很难对其进行剖析；在体外，观察到M2标记蛋白表达量低或无选择性，同样难以剖析。为了给体内巨噬细胞表型的复杂性提供基础，我们对小鼠M0、M1和M2巨噬细胞的转录特征进行了全面分析，并确定了每个亚群共有的或特有的基因。我们通过实时定量PCR验证了CD38、G蛋白偶联受体18（Gpr18）和甲酰肽受体2（Fpr2）为M1特异性表达模式，而早期生长反应蛋白2（Egr2）和c - Myc为M2特异性。我们通过流式细胞术进一步证实了这些数据，并表明M1和M2巨噬细胞可通过其CD38和Egr2的相对表达来区分。Egr2标记的M2巨噬细胞（约70%）比经典的M2巨噬细胞标记物精氨酸酶 - 1（标记24%的M2巨噬细胞）更多。相反，CD38标记了大多数（71%）体外培养的M1巨噬细胞。在体内，脂多糖暴露后，类似的CD38⁺细胞群大量增加。总体而言，这项工作确定了M1和M2特有的和共有的特征，并提供了新颖且更好的工具来区分小鼠M1和M2巨噬细胞。
Classically (M1) and alternatively activated (M2) macrophages exhibit distinct phenotypes and functions. It has been difficult to dissect macrophage phenotypes in vivo, where a spectrum of macrophage phenotypes exists, and also in vitro, where low or non-selective M2 marker protein expression is observed. To provide a foundation for the complexity of in vivo macrophage phenotypes, we performed a comprehensive analysis of the transcriptional signature of murine M0, M1 and M2 macrophages and identified genes common or exclusive to either subset. We validated by real-time PCR an M1-exclusive pattern of expression for CD38, G-protein coupled receptor 18 (Gpr18) and Formyl peptide receptor 2 (Fpr2) whereas Early growth response protein 2 (Egr2) and c-Myc were M2-exclusive. We further confirmed these data by flow cytometry and show that M1 and M2 macrophages can be distinguished by their relative expression of CD38 and Egr2. Egr2 labeled more M2 macrophages (~70%) than the canonical M2 macrophage marker Arginase-1, which labels 24% of M2 macrophages. Conversely, CD38 labeled most (71%) in vitro M1 macrophages. In vivo, a similar CD38+ population greatly increased after LPS exposure. Overall, this work defines exclusive and common M1 and M2 signatures and provides novel and improved tools to distinguish M1 and M2 murine macrophages.