Glucocorticoids induce differentiation of monocytes towards macrophages that share functional and phenotypical aspects with erythroblastic island macrophages.
Glucocorticoids induce differentiation of monocytes towards macrophages that share functional and phenotypical aspects with erythroblastic island macrophages.
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DOI：
10.3324/haematol.2017.179341
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发表时间：
2018-03
期刊：
影响因子：
10.1
通讯作者：
van den Akker E
中科院分区：
文献类型：
--
作者：
Heideveld E;Hampton-O'Neil LA;Cross SJ;van Alphen FPJ;van den Biggelaar M;Toye AM;van den Akker E
成红细胞岛中典型的中央巨噬细胞在骨髓成红细胞分化、增殖和去核中起重要作用。需要方便的人体外模型来促进红细胞-巨噬细胞相互作用的研究。最近，我们证明了培养的单核细胞/巨噬细胞通过支持造血干细胞和祖细胞存活来增强体外红细胞生成。在此，我们描述了这些特定的巨噬细胞也支持红细胞生成。在补充有干细胞因子、促红细胞生成素、脂质和地塞米松的无血清培养基中培养的人单核细胞向表达CD 16、CD 163、CD 169、CD 206、CXCR 4和吞噬性TAM受体家族的巨噬细胞分化。表型上，它们类似于人骨髓和胎肝驻留巨噬细胞。这种分化依赖于糖皮质激素受体的激活。蛋白质组学研究证实，糖皮质激素受体活化使单核细胞分化为具有M2表型的抗炎组织巨噬细胞，称为GC-巨噬细胞。参与迁移、组织驻留和信号转导/受体活性的蛋白质上调，而溶酶体和水解酶活性GO类下调。在功能上，我们表明，GC-巨噬细胞是高度移动的，并可以相互作用，形成集群与红系细胞的所有分化阶段和吞噬驱逐核，重演方面的成红细胞岛屿。总之，糖皮质激素指导的单核细胞分化为巨噬细胞代表了一个方便的模型系统，研究红细胞-巨噬细胞的相互作用。
The classical central macrophage found in erythroblastic islands plays an important role in erythroblast differentiation, proliferation and enucleation in the bone marrow. Convenient human in vitro models to facilitate the study of erythroid-macrophage interactions are desired. Recently, we demonstrated that cultured monocytes/macrophages enhance in vitro erythropoiesis by supporting hematopoietic stem and progenitor cell survival. Herein, we describe that these specific macrophages also support erythropoiesis. Human monocytes cultured in serum-free media supplemented with stem cell factor, erythropoietin, lipids and dexamethasone differentiate towards macrophages expressing CD16, CD163, CD169, CD206, CXCR4 and the phagocytic TAM-receptor family. Phenotypically, they resemble both human bone marrow and fetal liver resident macrophages. This differentiation is dependent on glucocorticoid receptor activation. Proteomic studies confirm that glucocorticoid receptor activation differentiates monocytes to anti-inflammatory tissue macrophages with a M2 phenotype, termed GC-macrophages. Proteins involved in migration, tissue residence and signal transduction/receptor activity are upregulated whilst lysosome and hydrolase activity GO-categories are downregulated. Functionally, we demonstrate that GC-macrophages are highly mobile and can interact to form clusters with erythroid cells of all differentiation stages and phagocytose the expelled nuclei, recapitulating aspects of erythroblastic islands. In conclusion, glucocorticoid-directed monocyte differentiation to macrophages represents a convenient model system to study erythroid-macrophage interactions.