Shin Seung Ho, Jung Jinsei, Park Haeng Ran, Sim Nam Suk, Choi Jae Young, Bae Seong Hoon
Department of Otorhinolaryngology-Head and Neck Surgery, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, South Korea.
Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, South Korea.
Front Cell Neurosci. 2022 Apr 12;16:844480. doi: 10.3389/fncel.2022.844480. eCollection 2022.
Cochlea macrophages regulate cochlea inflammation and may harbors the potentials to protect hearing function from injury, including acoustic overstimulation. Cochlea macrophage numbers increase at 3-7 days after acoustic stimulation. However, the exact timing of macrophage infiltration and maturation from inflammatory monocytes is unclear. Furthermore, neutrophils may also be involved in this process. Therefore, in this study, we investigated time-dependent immune cell infiltration, macrophage transformation, and neutrophil involvement following acoustic stimulation. Flow cytometry and immunofluorescence were conducted in C-X3-C motif chemokine receptor 1 (CX3CR1) mice after acoustic overstimulation (at baseline and at 1, 2, 3, and 5 days after exposure to 120 dB for 1 h) to identify inflammatory monocytes in the cochlea. RNA-sequencing and quantitative polymerase chain reaction were performed to identify differentially expressed genes. Inflammatory monocytes infiltrated into the lower portion of the lateral wall within 2 days after acoustic overstimulation (dpn), followed by transformation into macrophages at 3-5 dpn CX3CR1 upregulation and Ly6C downregulation. In addition, inflammatory monocytes were aggregated inside the collecting venule only at 1 dpn. Neutrophils were not a major type of phagocyte during this response. The gene encoding C-C motif chemokine ligand 2 gene was significantly upregulated as early as 3 h after acoustic overstimulation. Given these results, treatment to control immune response after a noise-induced hearing loss should be applied as soon as possible.
耳蜗巨噬细胞调节耳蜗炎症，可能具有保护听力功能免受损伤的潜力，包括免受声学过度刺激的损伤。声学刺激后3至7天，耳蜗巨噬细胞数量增加。然而，炎性单核细胞向巨噬细胞浸润和成熟的确切时间尚不清楚。此外，中性粒细胞可能也参与了这一过程。因此，在本研究中，我们调查了声学刺激后免疫细胞浸润、巨噬细胞转化以及中性粒细胞参与的时间依赖性变化。对声学过度刺激（基线以及暴露于120分贝1小时后的第1、2、3和5天）后的C-X3-C基序趋化因子受体1（CX3CR1）小鼠进行流式细胞术和免疫荧光检测，以识别耳蜗中的炎性单核细胞。进行RNA测序和定量聚合酶链反应以鉴定差异表达基因。声学过度刺激后2天内，炎性单核细胞浸润到外侧壁下部，随后在第3至5天转化为巨噬细胞，CX3CR1上调，Ly6C下调。此外，仅在第1天，炎性单核细胞聚集在集合小静脉内。在此反应过程中，中性粒细胞不是主要的吞噬细胞类型。编码C-C基序趋化因子配体2基因的基因在声学过度刺激后3小时就显著上调。鉴于这些结果，噪声性听力损失后控制免疫反应的治疗应尽早应用。
