Modulation of Decidual Macrophage Polarization by Macrophage Colony-Stimulating Factor Derived from First-Trimester Decidual Cells Implication in Preeclampsia
Modulation of Decidual Macrophage Polarization by Macrophage Colony-Stimulating Factor Derived from First-Trimester Decidual Cells Implication in Preeclampsia
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DOI：
10.1016/j.ajpath.2015.12.021
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发表时间：
2016-05-01
影响因子：
6
通讯作者：
Huang, S. Joseph
中科院分区：
文献类型：
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作者：
Li, Min;Piao, Longzhu;Huang, S. Joseph
在人类妊娠期间，胎儿半同种异体移植物的免疫耐受发生在丰富的母体白细胞的存在下。在植入部位，巨噬细胞约占白细胞总数的20%，并作为组织重塑的主要介质。蜕膜巨噬细胞显示抗炎和促炎表型之间的平衡。然而，在先兆子痫中报告了向M1亚型的转变。粒细胞-巨噬细胞集落刺激因子（GM-CSF）和巨噬细胞集落刺激因子（M-CSF）分别是介导M1和M2极化的主要分化因子。先前，我们观察到以下情况：i）先兆子痫蜕膜含有过量的巨噬细胞和GM-CSF，ii）先兆子痫相关的促炎细胞因子IL-1 β和肿瘤坏死因子-α显著增强培养的无白细胞的妊娠早期蜕膜细胞（FTDC）中的GM-CSF和M-CSF表达，iii）FTDC分泌的GM-CSF使巨噬细胞向M1亚型极化。微环境是巨噬细胞表型的关键决定因素。因此，我们研究了FTDC分泌的M-CSF的促炎刺激及其在巨噬细胞发育中的作用。免疫荧光染色显示子痫前期蜕膜中M-CSF阳性蜕膜细胞数量增加。在FTDC中，IL-1 β和肿瘤坏死因子-α通过NF-κ B途径发出信号以诱导M-CSF产生，其作用如下：i）增强巨噬细胞的分化并提高巨噬细胞中的CD 163表达，ii）增加巨噬细胞吞噬能力，和iii）抑制巨噬细胞的信号调节蛋白a表达。这些结果表明，FTDC分泌的M-CSF调节蜕膜免疫平衡诱导M2巨噬细胞极化和吞噬能力，在促炎刺激。
During human pregnancy, immune tolerance of the fetal semiallograft occurs in the presence of abundant maternal leukocytes. At the implantation site, macrophages comprise approximately 20% of the leukocyte population and act as primary mediators of tissue remodeling. Decidual macrophages display a balance between anti-inflammatory and proinflammatory phenotypes. However, a shift to an M1 subtype is reported in preeclampsia. Granulocyte-macrophage colony-stimulating-factor (GM-CSF) and macrophage colony stimulating factor (M-CSF) are major differentiating factors that mediate M1 and M2 polarization, respectively. Previously, we observed the following: i) the preeclamptic decidua contains an excess of both macrophages and GM-CSF, ii) the preeclampsia-associated proinflammatory cytokines, IL-1 beta and tumor necrosis factor-alpha, markedly enhance GM-CSF and M-CSF expression in cultured Leukocyte-free first-trimester deciduaL cells (FTDCs), iii) FTDC-secreted GM-CSF polarizes macrophages toward an M1 subtype. The microenvironment is a key determinant of macrophage phenotype. Thus, we examined proinflammatory stimulation of FTDC-secreted M-CSF and its role in macrophage development. Immunofluorescence staining demonstrated elevated M-CSF positive decidual cell numbers in preeclamptic decidua. In FTDCs, IL-1 beta and tumor necrosis factor-alpha signal through the NF-kappa B pathway to induce M-CSF production, which does the following: i) enhances differentiation of and elevates CD163 expression in macrophages, ii) increases macrophage phagocytic capacity, and iii) inhibits signal-regulatory protein a expression by macrophages. These findings suggest that FTDC-secreted M-CSF modulates the decidual immune balance by inducing M2 macrophage polarization and phagocytic capacity in response to proinflammatory stimuli.