Evidence for a dynamic role for mononuclear phagocytes during endometrial repair and remodelling.

Evidence for a dynamic role for mononuclear phagocytes during endometrial repair and remodelling.
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DOI:
10.1038/srep36748
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发表时间:
2016-11-09
期刊:
影响因子:
4.6
通讯作者:
Gibson DA
Gibson DA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cousins FL;Kirkwood PM;Saunders PT;Gibson DA

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在女性中,子宫内膜破裂(如月经)的特征是高浓度的炎症介质和免疫细胞,在组织脱落期间占基质室的约40%。已知这些炎性细胞在组织破坏中起关键作用,但它们对子宫内膜快速无瘢痕修复的作用仍知之甚少。在目前的研究中,我们使用小鼠月经模型来研究单核吞噬细胞在子宫内膜修复和重塑过程中的动态变化。在MacGreen小鼠中模拟月经,以使CSF 1 R+单核吞噬细胞可视化。免疫组化显示CSF 1 R-EGFP+细胞和Ly 6 G+中性粒细胞的数量和位置的动态时空变化。流式细胞术证实在修复期间(24小时)GFP+细胞数量显著增加:流入的细胞为66% F4/80+Gr-1+和30% F4/80−Gr-1+。免疫染色鉴定了假定的“经典”单核细胞(GFP+F4/80−)、单核细胞衍生的巨噬细胞(GFP+F4/80+)和假定的组织驻留巨噬细胞(GFP-F4/80+)的不同群体,其分别定位于分解、修复和重塑区域。总的来说,这些数据提供了第一个令人信服的证据,支持不同群体的单核细胞/巨噬细胞在子宫内膜修复中的作用,并为未来研究这些细胞在无瘢痕愈合中的作用提供了平台。
In women, endometrial breakdown, which is experienced as menstruation, is characterised by high concentrations of inflammatory mediators and immune cells which account for ~40% of the stromal compartment during tissue shedding. These inflammatory cells are known to play a pivotal role in tissue breakdown but their contribution to the rapid scarless repair of endometrium remains poorly understood. In the current study we used a mouse model of menstruation to investigate dynamic changes in mononuclear phagocytes during endometrial repair and remodelling. Menstruation was simulated in MacGreen mice to allow visualisation of CSF1R+ mononuclear phagocytes. Immunohistochemistry revealed dynamic spatio-temporal changes in numbers and location of CSF1R-EGFP+ cells and Ly6G+ neutrophils. Flow cytometry confirmed a striking increase in numbers of GFP+ cells during repair (24 h): influxed cells were 66% F4/80+Gr-1+ and 30% F4/80−Gr-1+. Immunostaining identified distinct populations of putative ‘classical’ monocytes (GFP+F4/80−), monocyte-derived macrophages (GFP+F4/80+) and a stable population of putative tissue-resident macrophages (GFP-F4/80+) localised to areas of breakdown, repair and remodelling respectively. Collectively, these data provide the first compelling evidence to support a role for different populations of monocytes/macrophages in endometrial repair and provide the platform for future studies on the role of these cells in scarless healing.
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