Elevated activity and microglial expression of myeloperoxidase in demyelinated cerebral cortex in multiple sclerosis
Elevated activity and microglial expression of myeloperoxidase in demyelinated cerebral cortex in multiple sclerosis
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DOI：
10.1111/j.1750-3639.2007.00110.x
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发表时间：
2008-01-01
期刊：
影响因子：
6.4
通讯作者：
Love, Seth
中科院分区：
文献类型：
--
作者：
Gray, Elizabeth;Thomas, Taya L.;Love, Seth
最近的研究显示，进行性多发性硬化症（MS）患者存在广泛的皮质脱髓鞘。灰质病变的脱髓鞘与小胶质细胞的激活有关。巨噬细胞和小胶质细胞在白质髓磷脂吞噬过程中表达髓过氧化物酶（MPO）并产生活性氧。在本研究中，我们检测了大脑皮层小胶质细胞的激活程度，以及小胶质细胞的激活和MPO活性与皮层脱髓鞘的关系。21例经神经病理学证实的多发性硬化症，34例皮质病变，被用来评估小胶质细胞的激活。在脱髓鞘的MS皮层中，激活的小胶质细胞的HLA-DR免疫标记明显高于对照皮层，在MS队列中，在皮质病变中，激活的小胶质细胞的HLA-DR免疫标记明显高于匹配的非脱髓鞘皮质区域。在MS皮质匀浆中，皮质脱髓鞘与MPO活性显著升高相关。免疫组织化学显示，皮层斑块内cd68阳性的小胶质细胞（尤其是斑块边缘）存在MPO，但邻近非脱髓鞘皮质的小胶质细胞不存在MPO。多发性硬化症的皮质脱髓鞘与MPO活性增加有关，MPO由活化的小胶质细胞的cd68阳性亚群表达，这表明小胶质细胞产生活性氧可能参与皮质脱髓鞘。
Recent studies have revealed extensive cortical demyelination in patients with progressive multiple sclerosis (MS). Demyelination in gray matter lesions is associated with activation of microglia. Macrophages and microglia are known to express myeloperoxidase (MPO) and generate reactive oxygen species during myelin phagocytosis in the white matter. In the present study we examined the extent of microglial activation in the cerebral cortex and the relationship of microglial activation and MPO activity to cortical demyelination. Twenty-one cases of neuropathologically confirmed multiple sclerosis, with 34 cortical lesions, were used to assess microglial activation. HLA-DR immunolabeling of activated microglia was significantly higher in demyelinated MS cortex than control cortex and, within the MS cohort, was significantly greater within cortical lesions than in matched non-demyelinated areas of cortex. In homogenates of MS cortex, cortical demyelination was associated with significantly elevated MPO activity. Immunohistochemistry revealed MPO in CD68-positive microglia within cortical plaques, particularly toward the edge of the plaques, but not in microglia in adjacent non-demyelinated cortex. Cortical demyelination in MS is associated with increased activity of MPO, which is expressed by a CD68-positive subset of activated microglia, suggesting that microglial production of reactive oxygen species is likely to be involved in cortical demyelination.