Bone marrow-derived cells expressing Iba1 are constitutively present as resident tissue macrophages in the mouse cochlea
Bone marrow-derived cells expressing Iba1 are constitutively present as resident tissue macrophages in the mouse cochlea
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DOI：
10.1002/jnr.21625
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发表时间：
2008-06-01
影响因子：
4.2
通讯作者：
Ito, Juichi
中科院分区：
文献类型：
--
作者：
Okano, Takayuki;Nakagawa, Takayuki;Ito, Juichi
免疫介导的内耳疾病已被确定为一个临床实体；然而，内耳的先天免疫系统是一个鲜为人知的研究领域，具有很高的临床和免疫学重要性。虽然已经提出内耳存在常驻组织巨噬细胞，但存在一些争议。在本研究中，我们分析了耳蜗巨噬细胞的来源以及造血骨髓（BM）对耳蜗巨噬细胞募集的贡献。为了可视化BM来源细胞的定位，我们将基因标记为增强绿色荧光蛋白的造血干细胞移植到致死辐照的C57BL/6小鼠中，制成BM嵌合小鼠。采用免疫组织化学方法研究脑脊髓瘤来源细胞在小鼠耳蜗内的分布和特征。我们成功地鉴定了螺旋韧带和螺旋神经节中组织常驻巨噬细胞的组成性存在，这些巨噬细胞来源于BM，数量比以前报道的要多。此外，耳蜗巨噬细胞在几个月的稳态替代过程中逐渐发生转变，耳蜗巨噬细胞数量立即增加，以应对局部手术应激。本研究结果证实了耳蜗常驻和浸润性巨噬细胞的造血起源。我们的研究为内耳提供了新的解剖学和免疫学基础，表明耳蜗巨噬细胞可能是内耳疾病的治疗靶点。(c) 2008 Wiley-Liss, Inc。
Immune-mediated inner ear disorder has been well established as a clinical entity; however, the innate immune system of the inner ear is a poorly understood area of research with high clinical and immunological importance. Although the presence of resident tissue macrophages in the inner ear has been suggested, there has been some controversy. In this study, we analyzed the origin of cochlear resident macrophages and the contribution of hematopoietic bone marrow (BM) to the recruitment of macrophages in the cochlea. To visualize the localization of BM-derived cells, BM chimeric mice were made by transplantation of hernatopoietic stem cells, which were genetically labeled with enhanced green fluorescent protein, into lethally irradiated C57BL/6 mice. The distribution and characteristics of BM-derived cells in the mouse cochlea were studied immunohistochemically. We successfully identified the constitutive presence of tissue resident macrophages in the spiral ligament and spiral ganglion that are derived from BM in larger numbers than previously reported. Moreover, cochlear resident macrophages gradually turn over for several months during steady-state replacement by BM-derived cells, and the number of cochlear macrophages immediately increased in response to local surgical stress. The present findings demonstrate the hematopoietic origin of cochlear resident and infiltrating macrophages. Our study provides a novel anatomical and immunological basis for the inner ear and indicates that the cochlear resident macrophages would be a therapeutic target in inner ear disorders. (c) 2008 Wiley-Liss, Inc.