Section of Otolaryngology, Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.
Immunology, Genetics and Pathology - Biovis Platform, Uppsala University, Uppsala, Sweden.
Front Immunol. 2018 Feb 13;9:223. doi: 10.3389/fimmu.2018.00223. eCollection 2018.
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.
人类内耳通过血-迷路屏障分隔，在结缔组织、神经元和支持细胞中存在固有巨噬细胞[CD163、离子钙结合衔接分子 1（IBA1）和 CD68 阳性细胞]。在耳蜗的外侧壁，这些细胞经常作为血管周围巨噬细胞存在于血管附近。已经表明，巨噬细胞也可以从血液中的单核细胞募集到因噪声、耳毒性药物、衰老和白喉毒素诱导的毛细胞变性而受损和死亡的毛细胞。精确监测可能对于避免自我靶向至关重要。巨噬细胞生物学最近表明，固有组织巨噬细胞群体可能与循环巨噬细胞在根本上不同。我们在手术切除岩斜脑膜瘤以治疗压迫脑干的过程中，获得了经过伦理同意保留下来的独特人类耳蜗。使用针对 IBA1、TUJ1、CX3CL1 和 IV 型胶原的免疫荧光抗体以及超分辨率结构照明显微镜（SR-SIM）进行了分子和细胞特征分析，并结合了透射电子显微镜。超分辨率显微镜揭示了与螺旋神经节细胞密切相关的 IBA1 细胞的显著表型变体。监测附着在具有“突触样”特化和突起的神经元上的细胞。活跃的巨噬细胞偶尔迁移到受损的毛细胞附近。结果表明，人类听觉神经受到发达的固有巨噬细胞系统的监控和可能的神经营养刺激。这可能部分解释了为什么与大多数哺乳动物不同，人类听觉神经在去传入后仍能得到保护，这可以缓解无髓鞘神经体的损伤。这使得耳蜗植入成为可能，从而使深度耳聋患者受益。IBA1 细胞可能具有其他功能，如免疫调节、废物处理和神经再生。它们在未来基于干细胞的治疗中的作用需要进一步探索。
