CCR5 Blockade Promotes M2 Macrophage Activation and Improves Locomotor Recovery After Spinal Cord Injury in Mice
CCR5 Blockade Promotes M2 Macrophage Activation and Improves Locomotor Recovery After Spinal Cord Injury in Mice
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DOI：
10.1007/s10753-014-0014-z
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发表时间：
2015-02-01
期刊：
影响因子：
5.1
通讯作者：
He, Xijing
中科院分区：
文献类型：
--
作者：
Li, Fengtao;Cheng, Bin;He, Xijing
脊髓损伤（SCI）被认为主要与运动功能丧失有关，并导致激活中枢神经系统的多种细胞机制，试图修复受损的脊髓组织。趋化因子受体5 （Chemokine Receptor 5, CCR5）是嗜巨噬人免疫缺陷病毒的主要共受体，表达于单核/巨噬细胞、树突状细胞、活化T细胞和NK细胞的表面。近年来的研究表明CCR5在SCI中的重要作用，但其机制尚不清楚。在我们目前的研究中，CCR5阻断表现出髓磷脂分裂增加和SC修复过程增强。脊髓损伤后抗ccr5组CD4(+) T细胞、CD8(+) T细胞、Ly6G（+）中性粒细胞、CD11b（+）巨噬细胞数量均显著低于对照组。脊髓损伤后抗ccr5组IL-4、IL-13水平明显高于对照组。相应地，抗ccr5处理组与对照IgG组相比，表达Arg1或cd206的巨噬细胞数量增加。此外，CCR5阻断促进PPAR γ激活，并且CCR5阻断诱导的M2巨噬细胞数量增加在额外的PPAR γ拮抗剂治疗后均被逆转。总之，我们目前的工作提供了证据支持CCR5阻断促进M2巨噬细胞活化和改善小鼠脊髓损伤后运动恢复的概念。
Spinal cord injury (SCI) is considered to be primarily associated with loss of motor function and leads to activate diverse cellular mechanisms in the central nervous system to attempt to repair the damaged spinal cord tissue. Chemokine Receptor 5 (CCR5), a major co-receptor for macrophage-tropic human immunodeficiency viruses, is expressed on the surface of monocytes/macrophages, dendritic cells, activated T cells, and NK cells. Recent papers have indicated the important role of CCR5 in SCI, but the mechanism is still unknown. In our current study, CCR5 blockade displayed increased myelin sparring and enhanced SC repair process. The number of CD4(+) T cells, CD8(+) T cells, Ly6G(+) neutrophils and CD11b(+) macrophages were all significantly lower in the anti-CCR5 group than that in the control group after SCI. The IL-4 and IL-13 levels in anti-CCR5 group were markedly higher than that in control group after SCI. Correspondingly, the anti-CCR5-treated group showed increased numbers of Arg1- or CD206-expressing macrophages compared with the control IgG group. Furthermore, CCR5 blockade promoted PPAR gamma activation, and the increased numbers of M2 macrophages induced by CCR5 blockade were both reversed with additional PPAR gamma antagonist treatment. In conclusion, our present work provides evidence to support the concept that CCR5 blockade promotes M2 macrophage activation and improves locomotor recovery after SCI in mice.