Henkel Jenny S, Beers David R, Siklós László, Appel Stanley H
Department of Neurology, Methodist Research Institute, 6560 Fannin St., Suite # 902, Houston, TX 77030, USA.
Mol Cell Neurosci. 2006 Mar;31(3):427-37. doi: 10.1016/j.mcn.2005.10.016. Epub 2005 Dec 5.
We recently demonstrated increased dendritic cells (potent antigen-presenting cells) and MCP-1 (monocyte, T-cell, and dendritic cell attracting chemokine) levels in ALS spinal cord tissue. Additionally, we presented data suggesting that dendritic cells might be contributing to the pathogenesis. To determine whether MCP-1 and dendritic cells are present in the mSOD1 mouse and how early in the disease process they are involved, we examined mSOD1 and control spinal cord tissue at different ages using real-time RT-PCR and immunohistochemistry. Dendritic cells were present and transcripts elevated in mSOD1 spinal cord beginning at 110 days. MCP-1 mRNA and immunoreactivity were upregulated in mSOD1 neuronal and glial cells as early as 15 days, prior to any evidence of microglial activation. CD68+ cells were present at 39 days of age. Although it is not clear if these responses are protective or injurious, the early increased MCP-1 expression and CD68+ cell presence indicate early preexisting injury.
我们最近证明,肌萎缩侧索硬化症(ALS)脊髓组织中的树突状细胞(强大的抗原呈递细胞)和MCP-1(单核细胞、T细胞和树突状细胞趋化因子)水平升高。此外,我们提供的数据表明树突状细胞可能参与了发病机制。为了确定MCP-1和树突状细胞是否存在于mSOD1小鼠中以及它们在疾病过程的早期如何发挥作用,我们使用实时逆转录聚合酶链反应(RT-PCR)和免疫组织化学方法,检测了不同年龄的mSOD1小鼠和对照小鼠的脊髓组织。从110天开始,mSOD1小鼠脊髓中就存在树突状细胞且其转录本水平升高。早在15天,在小胶质细胞激活的任何迹象出现之前,mSOD1神经元和神经胶质细胞中的MCP-1 mRNA和免疫反应性就上调了。39日龄时出现CD68+细胞。虽然尚不清楚这些反应是保护性的还是有害的,但早期MCP-1表达增加和CD68+细胞的出现表明早期已存在损伤。