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.

内耳的感觉器官包含常驻巨噬细胞群，它们被募集到细胞损伤的部位。已知这种巨噬细胞吞噬垂死细胞的碎片，但是尚不了解巨噬细胞在耳部病理学中的全部作用。斑马鱼的侧线神经瘤包含的毛细胞与内耳中的毛细胞几乎相同，幼虫斑马鱼的光学清晰度可直接成像细胞相互作用。在这项研究中，我们使用幼虫斑马鱼来表征巨噬细胞对侧线毛细胞耳毒性损伤的反应。巨噬细胞在暴露于耳毒性抗生素新霉素后20分钟内迁移到神经瘤中。受伤的神经质附近的巨噬细胞数量与未受伤的神经质附近的巨噬细胞数量相似，提示这种早期炎症反应是由“局部”巨噬细胞介导的。进入受伤的神经质后，巨噬细胞会主动吞噬毛细胞碎片。巨噬细胞的损伤诱发的迁移通过抑制Src家族激酶而显着降低。在耳毒性损伤之前使用巨噬细胞的化学遗传消融，我们还检查了巨噬细胞对于毛细胞再生的启动是否必不可少。结果显示，在巨噬细胞耗竭的鱼类和对照鱼中，毛细胞的恢复只有很小的差异，这表明巨噬细胞对于侧线毛细胞的再生不是必需的。巨噬细胞的损伤诱发的迁移通过抑制Src家族激酶而显着降低。在耳毒性损伤之前使用巨噬细胞的化学遗传消融，我们还检查了巨噬细胞对于毛细胞再生的启动是否必不可少。结果显示，在巨噬细胞耗竭的鱼类和对照鱼中，毛细胞的恢复只有很小的差异，这表明巨噬细胞对于侧线毛细胞的再生不是必需的。巨噬细胞的损伤诱发的迁移通过抑制Src家族激酶而显着降低。在耳毒性损伤之前使用巨噬细胞的化学遗传消融，我们还检查了巨噬细胞对于毛细胞再生的启动是否必不可少。结果显示，在巨噬细胞耗竭的鱼类和对照鱼中，毛细胞的恢复只有很小的差异，这表明巨噬细胞对于侧线毛细胞的再生不是必需的。