T cells contribute to lysophosphatidylcholine-induced macrophage activation and demyelination in the CNS
T cells contribute to lysophosphatidylcholine-induced macrophage activation and demyelination in the CNS
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DOI：
10.1002/glia.20449
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发表时间：
2007-02-01
期刊：
影响因子：
6.2
通讯作者：
David, Samuel
中科院分区：
文献类型：
--
作者：
Ghasemlou, Nader;Jeong, Suh Young;David, Samuel
我们之前的研究表明，脊髓内显微注射溶血磷脂酰碱（LPC），一种有效的脱髓鞘剂，会导致T细胞快速而短暂的涌入（在6到12小时之间）。这伴随着巨噬细胞/小胶质细胞的强烈激活，导致48小时的脱髓鞘。在本研究中，我们通过将LPC注射到缺乏T细胞的胸腺裸小鼠的背柱白质中，研究了T细胞的短暂流入是否有助于巨噬细胞/小胶质细胞的激活和脱髓鞘。我们发现，与野生型对照相比，裸鼠注射LPC后巨噬细胞/小胶质细胞活化和髓磷脂清除率显著降低。我们还发现，两种小鼠品系注射LPC后，造血巨噬细胞在脊髓内的募集没有差异。在被评估的T细胞因子中，与野生型动物相比，裸鼠的白细胞介素-2 (IL-2) mRNA表达明显减少。在野生型动物中，用功能阻断抗体中和IL-2可显著减少吞噬巨噬细胞/小胶质细胞的数量，并减少LPC诱导的脱髓鞘。虽然裸鼠中可能存在其他缺陷，可能导致此处所示的效果，但这些数据表明，T细胞在化学诱导脱髓鞘模型中的短暂内流可能在巨噬细胞/小胶质细胞激活和脱髓鞘中发挥作用。这些结果也可能对这种和其他类型的中枢神经系统损伤的髓鞘再生有启示。(c) 2006 Wiley-Liss, Inc。
We have previously shown that intraspinal microinjection of lysophosphatidyleholine (LPC), a potent demyelinating agent, results in a rapid but brief influx of T cells (between 6 and 12 h). This is accompanied by a robust activation of macrophages/microglia that leads to demyelination by 48 h. In the present study, we examined whether this brief influx of T cells contributes to the activation of macrophages/microglia and demyelination by injecting LPC into the dorsal column white matter of athymic Nude mice that lack T cells. We show that there is a significant reduction in macrophage/microglial activation and myelin clearance after LPC injection in Nude mice as compared with wildtype controls. We also show that there is no difference in the recruitment of hematogenous macrophages into the spinal cord after LPC injection in the two mouse strains. Of the T cell cytokines assessed, there was a marked reduction in the mRNA expression of interleukin-2 (IL-2) in Nude mice compared with wildtype animals. Neutralizing IL-2 with function-blocking antibodies in wildtype animals resulted in a significant decrease in the number of phagocytic macrophages/microglia and a reduction in demyelination induced by LPC. While there may be other defects in Nude mice that might contribute to the effects shown here, these data suggest that the brief influx of T cells in this model of chemically-induced demyelination could play a role in macrophage/microglial activation and demyelination. These results may also have implications for remyelination in this and other types of CNS damage. (c) 2006 Wiley-Liss, Inc.