趋化因子受体 CCR2 对慢性化脓性中耳炎患者的外耳道毛细胞具有保护作用

Q3 Medicine
Ankur Gupta, Viktoria Schiel, Ritwija Bhattacharya, Kourosh Eftekharian, Anping Xia, Peter L Santa Maria
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引用次数: 0

摘要

慢性化脓性中耳炎(CSOM)是一种被忽视的疾病,困扰着全球 3.3 亿人,是发展中国家儿童永久性听力损失的最常见原因。在此之前,我们发现外毛细胞(OHC)的损失发生在耳蜗的基底转折处,而巨噬细胞是与 CSOM 中外毛细胞损失相关的主要免疫细胞。巨噬细胞相关细胞因子上调。具体来说,CCL-2是MCP家族的重要成员,在中耳感染后会长期升高。CCR2 是 MCP 家族的共同受体,也是 CCL2 的独特受体。CCR2 基因敲除小鼠(CCR2-/-)已被广泛用于神经退行性疾病中单核细胞活化的研究。在本研究中,我们研究了 CCR2 缺失对 CSOM 耳蜗免疫反应和 OHC 存活率的影响。CCR2+/+CSOM耳蜗基转的OHC存活率为84±12.5%,而CCR2-/-CSOM耳蜗基转的OHC存活率为63±19.9%(P≤0.05)。与 CCR2+/+ CSOM 耳蜗相比,CCR2-/-CSOM 耳蜗中巨噬细胞的数量明显减少(p ≤ 0.001)。此外,CCR2-/-CSOM耳蜗中CCL7上调,而IL-33下调。最后,与 CCR2+/+ CSOM 相比,CCR2-/- CSOM 血管纹中血-迷宫屏障的通透性保持不变。总之,这些数据表明,CCR2 通过耳蜗巨噬细胞在 CSOM 耳蜗中发挥着保护作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Chemokine Receptor CCR2 Is Protective toward Outer Hair Cells in Chronic Suppurative Otitis Media.

Chronic suppurative otitis media (CSOM) is a neglected disease that afflicts 330 million people worldwide and is the most common cause of permanent hearing loss among children in the developing world. Previously, we discovered that outer hair cell (OHC) loss occurred in the basal turn of the cochlea and that macrophages are the major immune cells associated with OHC loss in CSOM. Macrophage-associated cytokines are upregulated. Specifically, CCL-2, an important member of the MCP family, is elevated over time following middle ear infection. CCR2 is a common receptor of the MCP family and the unique receptor of CCL2. CCR2 knockout mice (CCR2-/-) have been used extensively in studies of monocyte activation in neurodegenerative diseases. In the present study, we investigated the effect of CCR2 deletion on the cochlear immune response and OHC survival in CSOM. The OHC survival rate was 84 ± 12.5% in the basal turn of CCR2+/+ CSOM cochleae, compared with was 63 ± 19.9% in the basal turn of CCR2-/- CSOM cochleae (p ≤ 0.05). Macrophage numbers were significantly reduced in CCR2-/- CSOM cochleae compared with CCR2+/+ CSOM cochleae (p ≤ 0.001). In addition, CCL7 was upregulated, whereas IL-33 was downregulated, in CCR2-/- CSOM cochleae. Finally, the permeability of the blood-labyrinth barrier in the stria vascularis remained unchanged in CCR2-/- CSOM compared with CCR2+/+ CSOM. Taken together, the data suggest that CCR2 plays a protective role through cochlear macrophages in the CSOM cochlea.

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来源期刊
CiteScore
3.70
自引率
0.00%
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审稿时长
4 weeks
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