Macrophage recruitment and epithelial repair following hair cell injury in the mouse utricle.
Macrophage recruitment and epithelial repair following hair cell injury in the mouse utricle.
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DOI：
10.3389/fncel.2015.00150
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发表时间：
2015
影响因子：
5.3
通讯作者：
Warchol ME
中科院分区：
文献类型：
--
作者：
Kaur T;Hirose K;Rubel EW;Warchol ME
内耳的感觉器官拥有常驻的巨噬细胞群，但人们对这些细胞的功能知之甚少。在许多组织中，巨噬细胞参与损伤后细胞碎片的清除，还可以促进组织修复。本研究检查了小鼠椭圆囊中损伤诱发的巨噬细胞活性。实验使用了转基因小鼠，其中在 Pou4f3 启动子的调控下插入了人白喉毒素受体 (huDTR) 的基因。通过白喉毒素（DT）的全身治疗，可以选择性地损害这些小鼠的毛细胞。为了观察巨噬细胞，Pou4f3-huDTR 小鼠与第二个转基因品系杂交，其中 fractalkine 受体 CX3CR1 基因的一个或两个拷贝被 GFP 基因替换。这些小鼠在所有巨噬细胞中都表达 GFP，而 CX3CR1GFP/GFP 小鼠则缺乏 fractalkine 信号传导所需的受体。 DT 治疗导致 7 天内 70% 的椭圆囊毛细胞死亡，同时椭圆囊感觉上皮内巨噬细胞数量增加。许多巨噬细胞似乎正在积极吞噬毛细胞碎片，这表明巨噬细胞参与了哺乳动物前庭器官的“尸体清除”过程。然而，我们观察到 CX3CR1+/GFP 小鼠与 CX3CR1GFP/GFP 小鼠的椭圆囊中损伤诱发的巨噬细胞数量没有明显差异，这表明 fractalkine 信号对于这些感觉器官中巨噬细胞的募集不是必需的。最后，我们发现 DT 诱导的毛细胞损伤后短时间内感觉上皮的修复是由相对较细的 F-肌动蛋白线介导的。然而，恢复 56 天后，所有细胞与细胞的连接处都出现了非常粗的肌动蛋白电缆。
The sensory organs of the inner ear possess resident populations of macrophages, but the function of those cells is poorly understood. In many tissues, macrophages participate in the removal of cellular debris after injury and can also promote tissue repair. The present study examined injury-evoked macrophage activity in the mouse utricle. Experiments used transgenic mice in which the gene for the human diphtheria toxin receptor (huDTR) was inserted under regulation of the Pou4f3 promoter. Hair cells in such mice can be selectively lesioned by systemic treatment with diphtheria toxin (DT). In order to visualize macrophages, Pou4f3–huDTR mice were crossed with a second transgenic line, in which one or both copies of the gene for the fractalkine receptor CX3CR1 were replaced with a gene for GFP. Such mice expressed GFP in all macrophages, and mice that were CX3CR1GFP/GFP lacked the necessary receptor for fractalkine signaling. Treatment with DT resulted in the death of ∼70% of utricular hair cells within 7 days, which was accompanied by increased numbers of macrophages within the utricular sensory epithelium. Many of these macrophages appeared to be actively engulfing hair cell debris, indicating that macrophages participate in the process of ‘corpse removal’ in the mammalian vestibular organs. However, we observed no apparent differences in injury-evoked macrophage numbers in the utricles of CX3CR1+/GFP mice vs. CX3CR1GFP/GFP mice, suggesting that fractalkine signaling is not necessary for macrophage recruitment in these sensory organs. Finally, we found that repair of sensory epithelia at short times after DT-induced hair cell lesions was mediated by relatively thin cables of F-actin. After 56 days recovery, however, all cell-cell junctions were characterized by very thick actin cables.
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影响因子：
5.3
作者：
Lahne, Manuela;Gale, Jonathan E.
通讯作者：
Gale, Jonathan E.
DOI：
10.1523/jneurosci.2057-11.2011
发表时间：
2011-10-26
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Lin V;Golub JS;Nguyen TB;Hume CR;Oesterle EC;Stone JS
通讯作者：
Stone JS
影响因子：
4.4
作者：
Ishida, Yuko;Gao, Ji-Liang;Murphy, Philip M.
通讯作者：
Murphy, Philip M.
影响因子：
5.3
作者：
Jung, S;Aliberti, J;Littman, DR
通讯作者：
Littman, DR
影响因子：
9.2
作者：
Gale, JE;Piazza, V;Mammano, F
通讯作者：
Mammano, F