Identification of different macrophage subpopulations with distinct activities in a mouse model of oxygen-induced retinopathy.
Identification of different macrophage subpopulations with distinct activities in a mouse model of oxygen-induced retinopathy.
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氧诱导视网膜病变小鼠模型中具有不同活性的不同巨噬细胞亚群的鉴定
DOI：
10.3892/ijmm.2017.3022
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发表时间：
2017-08
影响因子：
5.4
通讯作者：
Xie B
中科院分区：
文献类型：
--
作者：
Zhu Y;Zhang L;Lu Q;Gao Y;Cai Y;Sui A;Su T;Shen X;Xie B
本研究的目的是表征氧诱导视网膜病变（OIR）小鼠模型中视网膜巨噬细胞不同亚群的表型转移、数量和作用变化。RT-qPCR分析巨噬细胞M1、M2亚群标记基因及极化相关基因mRNA表达水平。流式细胞术检测小鼠OIR模型中不同时间点的M1、M2巨噬细胞数量。采用OIR免疫荧光法在不同时间点对小鼠视网膜进行全载染色，观察巨噬细胞的内流情况，以及M1、M2巨噬细胞的形态特征和作用。由于促炎微环境中含有高水平的细胞粘附和白细胞跨内皮迁移分子，在OIR小鼠视网膜血管生成的过程中，巨噬细胞数量增加。不同时间点的RT-qPCR和流式细胞术分析显示，OIR小鼠的M1细胞数量从出生后13天的显著高水平下降到P21的相对正常水平，而M2细胞数量从P13增加到P21，提示巨噬细胞极化向M2亚型转移。免疫荧光染色显示，M1细胞与血管前方的内皮尖端细胞相互作用，M2细胞拥抱新生血管并桥接邻近的血管芽。因此，我们的数据表明巨噬细胞通过促进新血管形成的不同步骤在OIR中发挥积极作用。我们的研究结果表明，组织巨噬细胞可能被认为是眼部新生血管疾病抗血管生成治疗的潜在靶点。
The aim of the present study was to characterize the phenotypic shift, quantity and role changes in different subgroups of retinal macrophages in a mouse model of oxygen-induced retinopathy (OIR). The mRNA expression levels of macrophage M1 and M2 subgroup marker genes and polarization-associated genes were analyzed by RT-qPCR. The number of M1 and M2 macrophages in our mouse model of OIR was analyzed by flow cytometry at different time points during the progression of OIR. Immunofluorescence whole mount staining of the retinas of mice with OIR was performed at different time points to examine the influx of macrophages, as well as the morphological characteristics and roles of M1 and M2 macrophages. An increased number of macrophages was recruited during the progression of angiogenesis in the retinas of mice with OIR due to the pro-inflammatory microenvironment containing high levels of cell adhesion and leukocyte transendothelial migration molecules. RT-qPCR and flow cytometric analysis at different time points revealed a decline in the number of M1 cells from a significantly high level at post-natal day (P)13 to a relatively normal level at P21, as well as an increase in the number of M2 cells from P13 to P21 in the mice with OIR, implicating a shift of macrophage polarization towards the M2 subtype. Immunofluorescence staining suggested that the M1 cells interacted with endothelial tip cells at the vascular front, while M2 cells embraced the emerging vessels and bridged the neighboring vessel sprouts. Thus, our data indicate that macrophages play an active role in OIR by contributing to the different steps of neovascularization. Our findings indicate that tissue macrophages may be considered as a potential target for the anti-angiogenic therapy of ocular neovascularization disease.
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影响因子：
15.8
作者：
Apte, Rajendra S.;Richter, Jennifer;Herndon, John;Ferguson, Thomas A.
通讯作者：
Ferguson, Thomas A.
DOI：
10.1038/nrm3176
发表时间：
2011-08-23
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
2.6
作者：
Dace, Dru S.;Apte, Rajendra S.
通讯作者：
Apte, Rajendra S.
影响因子：
20.3
作者：
Fantin, Alessandro;Vieira, Joaquim M.;Ruhrberg, Christiana
通讯作者：
Ruhrberg, Christiana