Development of macrophages with altered actin organization in the absence of MafB
Development of macrophages with altered actin organization in the absence of MafB
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DOI：
10.1128/mcb.00245-06
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发表时间：
2006-09-01
影响因子：
5.3
通讯作者：
Sieweke, Michael H.
中科院分区：
文献类型：
--
作者：
Aziz, Athar;Vanhille, Laurent;Sieweke, Michael H.
在造血系统中，bZip转录因子MafB在单核细胞和巨噬细胞中以高水平选择性表达，并促进骨髓祖细胞中的巨噬细胞分化，而显性负等位基因可以抑制该过程。为了分析MafB对巨噬细胞发育的需求，我们产生了MafB缺陷小鼠，并且由于其新生儿致死表型，分析了体外、胚胎和重建小鼠中的巨噬细胞分化。令人惊讶的是，我们观察到来自E14.5胎肝（FL）细胞和E18.5脾细胞的巨噬细胞的体外分化。此外，我们在胎儿肝脏、脾脏和血液以及成年MafB（-/-）FL重建小鼠的骨髓、脾脏和腹膜中发现了正常数量的F4/80（+）/Mac-1（+）巨噬细胞和单核细胞。MafB（-/-）巨噬细胞显示出完整的基本巨噬细胞功能，例如对乳胶珠或单核细胞增生李斯特菌的吞噬作用以及响应于脂多糖的一氧化氮产生。相比之下，MafB（-/-）巨噬细胞表达了参与肌动蛋白组织的多个基因的增加水平。与此一致，鬼笔环肽染色揭示了改变的形态，涉及响应于巨噬细胞集落刺激因子的MafB（-/-）巨噬细胞的分支突起的数量增加。这些数据共同指出了MafB在巨噬细胞分化中的意外冗余功能以及在肌动蛋白依赖性巨噬细胞形态中的先前未知作用。
In the hematopoietic system the bZip transcription factor MafB is selectively expressed at high levels in monocytes and macrophages and promotes macrophage differentiation in myeloid progenitors, whereas a dominant-negative allele can inhibit this process. To analyze the requirement of MafB for macrophage development, we generated MafB-deficient mice and, due to their neonatal lethal phenotype, analyzed macrophage differentiation in vitro, in the embryo, and in reconstituted mice. Surprisingly we observed in vitro differentiation of macrophages from E14.5 fetal liver (FL) cells and E18.5 splenocytes. Furthermore we found normal numbers of F4/80(+)/Mac-1(+) macrophages and monocytes in fetal liver, spleen, and blood as well as in bone marrow, spleen, and peritoneum of adult MafB(-/-) FL reconstituted mice. MafB(-/-) macrophages showed intact basic macrophage functions such as phagocytosis of latex beads or Listeria monocytogenes and nitric oxide production in response to lipopolysaccharide. By contrast, MafB(-/-) macrophages expressed increased levels of multiple genes involved in actin organization. Consistent with this, phalloidin staining revealed an altered morphology involving increased numbers of branched protrusions of MafB(-/-) macrophages in response to macrophage colony-stimulating factor. Together these data point to an unexpected redundancy of MafB function in macrophage differentiation and a previously unknown role in actin-dependent macrophage morphology.