Presence of dendritic cells, MCP-1, and activated microglia/macrophages in amyotrophic lateral sclerosis spinal cord tissue
Presence of dendritic cells, MCP-1, and activated microglia/macrophages in amyotrophic lateral sclerosis spinal cord tissue
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DOI：
10.1002/ana.10805
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发表时间：
2004-02-01
影响因子：
11.2
通讯作者：
Appel, SH
中科院分区：
文献类型：
--
作者：
Henkel, JS;Engelhardt, JI;Appel, SH
树突状细胞是一种有效的抗原呈递细胞，可以启动和增强免疫反应。为了确定树突状细胞是否参与肌萎缩侧索硬化（ALS）的炎症反应，我们采用半定量和实时逆转录聚合酶链反应（RT-PCR）检测了个体散发性ALS（sALS）、家族性ALS（fALS）和非神经疾病对照（NNDC）脊髓组织中树突状细胞表面标志物的mRNA表达。ALS组织中未成熟（DEC 205，CD 1a）和活化/成熟（CD 83，CD 40）树突状细胞转录物显著升高。免疫组化证实ALS腹角和皮质脊髓束中存在未成熟和活化/成熟的树突状细胞（CD 1a（+）和CD 83（+））。ALS脊髓中单核细胞/巨噬细胞/小胶质细胞转录物（CD 14、CD 18、SR-A、CD 68）增加，并且在运动神经元附近显示活化的CD 68（+）细胞。趋化因子MCP-1的mRNA表达，吸引单核细胞和骨髓树突状细胞，和细胞因子巨噬细胞集落刺激因子（M-CSF）在ALS组织中增加。MCP-1蛋白在ALS患者的神经胶质中表达，但在对照组织中不表达，并且在ALS患者的CSF中表达增加。那些进展最快的患者比进展较慢的患者表达更多的树突状转录本。这些结果支持免疫/炎症反应参与放大ALS中的运动神经元变性。
Dendritic cells are potent antigen-presenting cells that initiate and amplify immune responses. To determine whether dendritic cells participate in inflammatory reactions in amyotrophic lateral sclerosis (ALS), we examined mRNA expression of dendritic cell surface markers in individual sporadic ALS (sALS), familial ALS (fALS), and nonneurological disease control (NNDC) spinal cord tissues using semiquantitative and real-time reverse transcription polymerase chain reaction (RT-PCR). Immature (DEC205, CD1a) and activated/mature (CD83, CD40) dendritic cell transcripts were significantly elevated in ALS tissues. The presence of immature and activated/mature dendritic cells (CD1a(+) and CD83(+)) was confirmed immunohistochemically in ALS ventral horn and corticospinal tracts. Monocytic/macrophage/microglial transcripts (CD14, CD18, SR-A, CD68) were increased in ALS spinal cord, and activated CD68(+) cells were demonstrated in close proximity to motor neurons. mRNA expressions of the chemokine MCP-1, which attracts monocytes and myeloid dendritic cells, and of the cytokine macrophage-colony stimulating factor (M-CSF) were increased in ALS tissues. The MCP-1 protein was expressed in glia in ALS but not in control tissues and was increased in the CSF of ALS patients. Those patients who progressed most rapidly expressed significantly more dendritic transcripts than patients who progressed more slowly. These results support the involvement of immune/inflammatory responses in amplifying motor neuron degeneration in ALS.