Molecular and cellular identification of the immune response in peripheral ganglia following nerve injury.
Molecular and cellular identification of the immune response in peripheral ganglia following nerve injury.
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DOI：
10.1186/s12974-018-1222-5
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发表时间：
2018-06-26
影响因子：
9.3
通讯作者：
Zigmond RE
中科院分区：
文献类型：
--
作者：
Lindborg JA;Niemi JP;Howarth MA;Liu KW;Moore CZ;Mahajan D;Zigmond RE
神经炎症伴随神经创伤和大多数神经系统疾病。周围神经系统（PNS）中的轴突切断术导致受损神经元的显著变化：细胞体表达一组独特的基因，称为再生相关基因，远端轴突节段退化，其碎片被清除，近端节段中的轴突形成生长锥并延伸神经突。这些过程部分是由免疫细胞和其他非神经元细胞协调的。神经节中的巨噬细胞在支持再生中起着不可或缺的作用。在这里，我们进一步探讨外周神经节内损伤诱导的免疫反应的分子和细胞成分。对成年雄性野生型（WT）和Ccr 2 −/−小鼠进行坐骨神经单侧横断和上级颈神经节（SCG）轴突切断术。用抗体芯片检测背根神经节（DRG）和上神经节（SCG）中趋化因子和细胞因子的表达。利用流式细胞术和免疫组织化学来鉴定神经节内损伤诱导的免疫反应的细胞组成。神经损伤后48 h，神经节中的趋化因子表达不同，SCG中的巨噬细胞炎性蛋白-1 γ大量增加，但DRG中没有，而C-C类趋化因子配体2在两个神经节中均高度表达。WT和Ccr 2 −/−小鼠之间的差异也被观察到，与C-C类趋化因子受体2（CCR 2）−/− DRG相比，WT DRG中C-C类趋化因子配体6/C10表达增加，与WT相比，CCR 2 −/− SCG中CXCL 5表达增加。神经损伤后7天，与WT神经节相比，发现Ccr 2 −/−小鼠DRG和SCG中的巨噬细胞蓄积减少。有趣的是，在SCG中发现了中性粒细胞，但在DRG中没有。损伤后7天测量的细胞因子表达在神经节类型和基因型之间存在差异。巨噬细胞的活化测定与抗炎标志物CD 206和巨噬细胞标志物CD 68的colabeling神经节，和几乎完全共定位的两个标志物被发现在两个神经节。这项研究证明了DRG和SCG之间以及WT和Ccr 2 −/−小鼠之间神经损伤诱导的免疫反应的分子和细胞差异。
Neuroinflammation accompanies neural trauma and most neurological diseases. Axotomy in the peripheral nervous system (PNS) leads to dramatic changes in the injured neuron: the cell body expresses a distinct set of genes known as regeneration-associated genes, the distal axonal segment degenerates and its debris is cleared, and the axons in the proximal segment form growth cones and extend neurites. These processes are orchestrated in part by immune and other non-neuronal cells. Macrophages in ganglia play an integral role in supporting regeneration. Here, we explore further the molecular and cellular components of the injury-induced immune response within peripheral ganglia. Adult male wild-type (WT) and Ccr2−/− mice were subjected to a unilateral transection of the sciatic nerve and axotomy of the superior cervical ganglion (SCG). Antibody arrays were used to determine the expression of chemokines and cytokines in the dorsal root ganglion (DRG) and SCG. Flow cytometry and immunohistochemistry were utilized to identify the cellular composition of the injury-induced immune response within ganglia. Chemokine expression in the ganglia differed 48 h after nerve injury with a large increase in macrophage inflammatory protein-1γ in the SCG but not in the DRG, while C-C class chemokine ligand 2 was highly expressed in both ganglia. Differences between WT and Ccr2−/− mice were also observed with increased C-C class chemokine ligand 6/C10 expression in the WT DRG compared to C-C class chemokine receptor 2 (CCR2)−/− DRG and increased CXCL5 expression in CCR2−/− SCG compared to WT. Diminished macrophage accumulation in the DRG and SCG of Ccr2−/− mice was found compared to WT ganglia 7 days after nerve injury. Interestingly, neutrophils were found in the SCG but not in the DRG. Cytokine expression, measured 7 days after injury, differed between ganglion type and genotype. Macrophage activation was assayed by colabeling ganglia with the anti-inflammatory marker CD206 and the macrophage marker CD68, and an almost complete colocalization of the two markers was found in both ganglia. This study demonstrates both molecular and cellular differences in the nerve injury-induced immune response between DRG and SCG and between WT and Ccr2−/− mice.
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