Macrophages in the Human Cochlea: Saviors or Predators-A Study Using Super-Resolution Immunohistochemistry.
Macrophages in the Human Cochlea: Saviors or Predators-A Study Using Super-Resolution Immunohistochemistry.
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DOI：
10.3389/fimmu.2018.00223
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发表时间：
2018
影响因子：
7.3
通讯作者：
Rask-Andersen H
中科院分区：
文献类型：
--
作者：
Liu W;Molnar M;Garnham C;Benav H;Rask-Andersen H
人内耳由血液/迷路屏障隔离，在结缔组织、神经元和支持细胞内含有常驻巨噬细胞[CD 163、离子化钙结合衔接分子1（IBA 1）和CD 68阳性细胞]。在耳蜗的外侧壁，这些细胞经常作为血管周围的巨噬细胞靠近血管。巨噬细胞也显示从血液传播的单核细胞募集到由噪音、耳毒性药物、衰老和白喉毒素诱导的毛细胞变性诱导的受损和垂死的毛细胞。精确监测对于避免自我瞄准可能至关重要。巨噬细胞生物学最近表明，常驻组织巨噬细胞的群体可能与循环巨噬细胞根本不同。我们在手术治疗岩斜区脑膜瘤压迫脑干时，在征得伦理同意后，切除了保存完好的人耳蜗。使用针对IBA 1，TUJ 1，CX 3CL 1和IV型胶原蛋白的抗体的免疫荧光和超分辨率结构照明显微镜（SR-SIM）与透射电子显微镜一起进行分子和细胞表征。超分辨率显微镜下发现了与螺旋神经节细胞密切相关的IBA 1细胞的显著表型变异。监测细胞粘附到具有“突触样”特化和突起的神经元上。活跃的巨噬细胞偶尔迁移到受损的毛细胞附近。结果表明，人类听神经是一个发达的居民巨噬细胞系统的监督和可能的神经营养刺激。无髓鞘神经索马可能会减轻这种情况，这部分解释了为什么与大多数哺乳动物相反，人类的听觉神经在去传入神经后会被保留。它使人工耳蜗植入成为可能，为深度耳聋的人带来好处。IBA 1细胞还可以用于其他目的，如免疫调节、废物处理和神经再生。它们在未来干细胞治疗中的作用需要进一步探索。
The human inner ear, which is segregated by a blood/labyrinth barrier, contains resident macrophages [CD163, ionized calcium-binding adaptor molecule 1 (IBA1)-, and CD68-positive cells] within the connective tissue, neurons, and supporting cells. In the lateral wall of the cochlea, these cells frequently lie close to blood vessels as perivascular macrophages. Macrophages are also shown to be recruited from blood-borne monocytes to damaged and dying hair cells induced by noise, ototoxic drugs, aging, and diphtheria toxin-induced hair cell degeneration. Precise monitoring may be crucial to avoid self-targeting. Macrophage biology has recently shown that populations of resident tissue macrophages may be fundamentally different from circulating macrophages. We removed uniquely preserved human cochleae during surgery for treating petroclival meningioma compressing the brain stem, after ethical consent. Molecular and cellular characterization using immunofluorescence with antibodies against IBA1, TUJ1, CX3CL1, and type IV collagen, and super-resolution structured illumination microscopy (SR-SIM) were made together with transmission electron microscopy. The super-resolution microscopy disclosed remarkable phenotypic variants of IBA1 cells closely associated with the spiral ganglion cells. Monitoring cells adhered to neurons with “synapse-like” specializations and protrusions. Active macrophages migrated occasionally nearby damaged hair cells. Results suggest that the human auditory nerve is under the surveillance and possible neurotrophic stimulation of a well-developed resident macrophage system. It may be alleviated by the non-myelinated nerve soma partly explaining why, in contrary to most mammals, the human’s auditory nerve is conserved following deafferentiation. It makes cochlear implantation possible, for the advantage of the profoundly deaf. The IBA1 cells may serve additional purposes such as immune modulation, waste disposal, and nerve regeneration. Their role in future stem cell-based therapy needs further exploration.