CC chemokine receptor 2 is protective against noise-induced hair cell death: studies in CX3CR1(+/GFP) mice.
CC chemokine receptor 2 is protective against noise-induced hair cell death: studies in CX3CR1(+/GFP) mice.
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DOI：
10.1007/s10162-006-0051-x
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发表时间：
2006-12
影响因子：
2.4
通讯作者：
Hirose, Keiko
中科院分区：
文献类型：
--
作者：
Sautter, Nathan B.;Shick, Elizabeth H.;Ransohoff, Richard M.;Charo, Israel F.;Hirose, Keiko
最近的研究表明，听觉创伤可引起耳内的炎症反应，其特征是巨噬细胞快速进入螺旋韧带。本研究旨在阐明巨噬细胞聚集到耳蜗外侧壁的机制，以及巨噬细胞在噪声损伤或修复中的作用。CCL2及其主要受体CCR2是体内单核细胞趋化最广泛证实的效应物。CCR2 - / -和CCR2 - / -小鼠已被广泛用于神经元损伤中单核细胞活化的研究。然而，CCL2和CCR2在耳蜗中的功能尚未被研究。本研究探讨了CCL2和CCR2在听觉损伤中的作用。将CX3CR1+/GFP背景下的CCL2 - / -和CCR2 - / -小鼠暴露于8-16 kHz的倍频带噪声中2小时，以确定CCL2和CCR2对单核细胞向耳蜗迁移、阈值移位和细胞存活的影响。我们发现，与背景菌株（CX3CR1+/GFP）相比，两种敲除小鼠菌株的阈值移位没有变化。令人惊讶的是，我们发现尽管缺乏CCL2或CCR2，单核细胞的迁移也没有改变。然而，在CCR2−/−菌株中，噪声诱导的毛细胞死亡显著增加。这一观察结果表明，CCR2独立于CCL2，在噪声后的耳蜗中起保护作用，单核细胞迁移不需要配体或受体。讨论了CCR2可能的神经保护机制。
Acoustic trauma was recently shown to induce an inflammatory response in the ear characterized by rapid entry of macrophages in the spiral ligament. The current study seeks to elucidate the mechanisms involved in summoning macrophages to the cochlear lateral wall and the role macrophages play in noise-induced injury or repair. CCL2 and its primary receptor, CCR2, are the most widely validated effectors of monocyte chemotaxis in vivo. CCL2−/− and CCR2−/− mice have been used extensively in studies of monocyte activation in neuronal injury. However, the function of CCL2 and CCR2 in the cochlea has not been studied. The present study examines the role of CCL2 and CCR2 in acoustic injury. CCL2−/− and CCR2−/− mice on a CX3CR1+/GFP background were exposed to octave band noise (8–16 kHz) for 2 h to determine the effect of CCL2 and CCR2 on monocyte migration into the cochlea, threshold shift, and cell survival. We found that threshold shift was unchanged in the two knockout mouse strains when compared to the background strain (CX3CR1+/GFP). Surprisingly, we found that monocyte migration was also unchanged, despite the absence of CCL2 or CCR2. However, there was a dramatic increase in noise-induced hair cell death in the CCR2−/− strain. This observation suggests that CCR2, independent of CCL2, plays a protective role in the cochlea after noise, and neither ligand nor receptor is necessary for monocyte migration. Possible mechanisms of neuroprotection by CCR2 are discussed.
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DOI：
10.1007/s101620020028
发表时间：
2002-09-01
期刊：
JARO
影响因子：
--
作者：
Wang, Y;Hirose, K;Liberman, MC
通讯作者：
Liberman, MC
DOI：
10.1016/s0169-328x(02)00158-4
发表时间：
2002-06-30
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Muessel, MJ;Klein, RM;Berman, NEJ
通讯作者：
Berman, NEJ
影响因子：
5.3
作者：
Jung, S;Aliberti, J;Littman, DR
通讯作者：
Littman, DR
影响因子：
5.3
作者：
Dzenko, KA;Andjelkovic, AV;Pachter, JS
通讯作者：
Pachter, JS
影响因子：
1.4
作者：
FREDELIUS, L
通讯作者：
FREDELIUS, L