Warchol Mark E, Schrader Angela, Sheets Lavinia
Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO, United States.
Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States.
Front Cell Neurosci. 2021 Jan 8;14:613246. doi: 10.3389/fncel.2020.613246. eCollection 2020.
The sensory organs of the inner ear contain resident populations of macrophages, which are recruited to sites of cellular injury. Such macrophages are known to phagocytose the debris of dying cells but the full role of macrophages in otic pathology is not understood. Lateral line neuromasts of zebrafish contain hair cells that are nearly identical to those in the inner ear, and the optical clarity of larval zebrafish permits direct imaging of cellular interactions. In this study, we used larval zebrafish to characterize the response of macrophages to ototoxic injury of lateral line hair cells. Macrophages migrated into neuromasts within 20 min of exposure to the ototoxic antibiotic neomycin. The number of macrophages in the near vicinity of injured neuromasts was similar to that observed near uninjured neuromasts, suggesting that this early inflammatory response was mediated by "local" macrophages. Upon entering injured neuromasts, macrophages actively phagocytosed hair cell debris. The injury-evoked migration of macrophages was significantly reduced by inhibition of Src-family kinases. Using chemical-genetic ablation of macrophages before the ototoxic injury, we also examined whether macrophages were essential for the initiation of hair cell regeneration. Results revealed only minor differences in hair cell recovery in macrophage-depleted vs. control fish, suggesting that macrophages are not essential for the regeneration of lateral line hair cells.
内耳的感觉器官含有常驻巨噬细胞群，这些巨噬细胞会被招募到细胞损伤部位。已知此类巨噬细胞会吞噬死亡细胞的碎片，但巨噬细胞在耳部病理学中的完整作用尚不清楚。斑马鱼的侧线神经丘含有与内耳中的毛细胞几乎相同的毛细胞，并且幼体斑马鱼的光学清晰度允许直接对细胞间相互作用进行成像。在本研究中，我们使用幼体斑马鱼来表征巨噬细胞对侧线毛细胞耳毒性损伤的反应。巨噬细胞在接触耳毒性抗生素新霉素后20分钟内迁移到神经丘中。受伤神经丘附近的巨噬细胞数量与未受伤神经丘附近观察到的数量相似，这表明这种早期炎症反应是由“局部”巨噬细胞介导的。巨噬细胞进入受伤的神经丘后，会积极吞噬毛细胞碎片。抑制Src家族激酶可显著减少损伤引起的巨噬细胞迁移。在耳毒性损伤前使用化学遗传学方法清除巨噬细胞，我们还研究了巨噬细胞对于毛细胞再生的起始是否必不可少。结果显示，巨噬细胞缺失的鱼与对照鱼在毛细胞恢复方面只有微小差异，这表明巨噬细胞对于侧线毛细胞的再生并非必不可少。
