Sato Eisuke, Shick H Elizabeth, Ransohoff Richard M, Hirose Keiko
Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
J Comp Neurol. 2008 Feb 20;506(6):930-42. doi: 10.1002/cne.21583.
Cochlear macrophages have been shown to accumulate in the murine cochlea following acoustic trauma. This investigation was performed to determine whether cochlear macrophages could be replaced by donor transplantation of bone marrow precursors. Lethally irradiated C57BL/6 mice were transplanted with hematopoietic precursors from CX3CR1(GFP/GFP) fetal mice. CX3CR1(GFP/GFP) mice express green fluorescent protein (GFP) in monocytes and macrophages and possess no functional CX3CR1. Donor monocytes and macrophages can be easily traced in the wild-type recipient with fluorescent microscopy. We studied mice at 2-16 weeks after transplantation to assess repopulation of cochlear macrophages. A separate group of chimeras was exposed to octave band noise (8-16 kHz for 2 hours) 2 weeks after transplantation to evaluate the migration properties of donor hematopoietic precursors. We found that macrophages derived from donor hematopoietic precursors appeared in cochlea 3-4 weeks after transplantation and increased week by week. Noise exposure induced a massive accumulation of leukocytes, particularly in the spiral ligament of the basal turn. There was no difference between CX3CR1(GFP/GFP) donor/wild-type recipient chimeras and the wild-type donor/wild-type recipient chimeras in hearing thresholds, accumulation of cochlear macrophages, or tissue injury after noise exposure. These data indicate that cochlear macrophages are derived from bone marrow precursors and that they are an exchanging and migratory population. Furthermore, CX3CR1 in hematopoietic precursors is not necessary for macrophage migration into cochlea and when deleted in this cell population, the absence of CX3CR1 does not substantially effect the outcomes after noise.
研究表明，声学创伤后小鼠耳蜗内会积聚巨噬细胞。本研究旨在确定耳蜗巨噬细胞是否可通过移植骨髓前体细胞进行替代。对C57BL/6小鼠进行致死剂量照射后，移植来自CX3CR1(GFP/GFP)胎鼠的造血前体细胞。CX3CR1(GFP/GFP)小鼠在单核细胞和巨噬细胞中表达绿色荧光蛋白(GFP)，且不具有功能性CX3CR1。通过荧光显微镜可轻松追踪野生型受体中供体单核细胞和巨噬细胞。我们在移植后2至16周对小鼠进行研究，以评估耳蜗巨噬细胞的重新填充情况。另一组嵌合体在移植后2周暴露于倍频程带噪声(8 - 16 kHz，持续2小时)，以评估供体造血前体细胞的迁移特性。我们发现，移植后3至4周，供体造血前体细胞衍生的巨噬细胞出现在耳蜗中，并逐周增加。噪声暴露导致白细胞大量积聚，尤其是在基底转的螺旋韧带中。在听力阈值、耳蜗巨噬细胞积聚或噪声暴露后的组织损伤方面，CX3CR1(GFP/GFP)供体/野生型受体嵌合体与野生型供体/野生型受体嵌合体之间没有差异。这些数据表明，耳蜗巨噬细胞来源于骨髓前体细胞，且它们是一个可交换和迁移的群体。此外，造血前体细胞中的CX3CR1对于巨噬细胞迁移到耳蜗并非必需，当该细胞群体中CX3CR1缺失时，其缺失对噪声后的结果没有实质性影响。
