The macrophage contribution to stress erythropoiesis: when less is enough.
The macrophage contribution to stress erythropoiesis: when less is enough.
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DOI：
10.1182/blood-2016-05-714527
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发表时间：
2016-09
期刊：
影响因子：
20.3
通讯作者：
T. Ulyanova;Susan R. Phelps;T. Papayannopoulou
中科院分区：
文献类型：
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作者：
T. Ulyanova;Susan R. Phelps;T. Papayannopoulou
虽然天然骨髓和脾巨噬细胞在增强基线和应激红细胞生成中的重要性已经被强调了几十年，但它们在各种应激反应期间的动力学和表型变化尚不清楚。此外，单核细胞来源的募集的巨噬细胞是否可以在功能上替代不足或功能受损的天然巨噬细胞一直存在争议，似乎不仅是组织依赖性的，而且也是应力类型依赖性的。为了进一步深入了解这些问题，我们在2种巨噬细胞数量遗传抑制的小鼠模型中进行了基线和红细胞后应激（E-应激）的详细观察，并将其与对照组进行了比较。我们记录了，无论应激诱导（溶血或促红细胞生成素[Epo]后）治疗，只有天然CD 11b（lo）脾巨噬细胞在正常小鼠应激后急剧扩增，单核细胞衍生的CD 11b（hi）亚群没有显著变化。后者仍然是少数，在缺乏Spi-C或VCAM-1的2个遗传模型中，没有改变应激后的天然巨噬细胞增殖扩张受损。尽管这些小鼠中的CD 11b（lo）巨噬细胞在其峰值反应时是正常的五分之一，但令人惊讶的是，它们的红细胞反应没有受到损害，并且与对照组相似。因此，尽管先前强调巨噬细胞依赖于数值来提供E-应激的功能性拯救，但我们的数据突出了先前描述的在某些应激条件下激活的非巨噬细胞依赖性途径的重要性，以补偿低巨噬细胞数。
Although the importance of native bone marrow and spleen macrophages in enhancing baseline and stress erythropoiesis has been emphasized over several decades, their kinetic and phenotypic changes during a variety of stress responses have been unclear. Furthermore, whether monocyte-derived recruited macrophages can functionally substitute for inadequate or functionally impaired native macrophages has been controversial and seem to be not only tissue- but also stress-type dependent. To provide further insight into these issues, we made detailed observations at baseline and post-erythroid stress (E-stress) in 2 mouse models with genetically depressed macrophage numbers and compared them to their controls. We documented that, irrespective of the stress-induced (hemolytic or post-erythropoietin [Epo]) treatment, only native CD11b(lo) splenic macrophages expand dramatically post-stress in normal mice without significant changes in the monocyte-derived CD11b(hi) subset. The latter remained a minority and did not change post-stress in 2 genetic models lacking either Spi-C or VCAM-1 with impaired native macrophage proliferative expansion. Although CD11b(lo) macrophages in these mice were one-fifth of normal at their peak response, surprisingly, their erythroid response was not compromised and was similar to controls. Thus, despite the prior emphasis on numerical macrophage reliance to provide functional rescue from E-stress, our data highlight the importance of previously described non-macrophage-dependent pathways activated under certain stress conditions to compensate for low macrophage numbers.