Increased 14-3-3 immunoreactivity in glial elements in patients with multiple sclerosis
Increased 14-3-3 immunoreactivity in glial elements in patients with multiple sclerosis
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DOI：
10.1007/s00401-003-0785-z
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发表时间：
2004-02-01
影响因子：
12.7
通讯作者：
Budka, H
中科院分区：
文献类型：
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作者：
Kawamoto, Y;Akiguchi, I;Budka, H
14-3-3蛋白已被证明在患有多种神经系统疾病（包括多发性硬化症（MS））的患者的脑脊液中增加。为了研究14-3-3蛋白是否与MS的发病机制密切相关，我们对10例MS患者、5例进行性多灶性白质脑病（PML）患者和7例正常对照者的尸检脑组织中的14-3-3进行了免疫组织化学研究。所有病例的福尔马林固定、石蜡包埋切片用特异性抗14-3-3抗体进行免疫染色，MS病例的一些切片用抗14-3-3和神经胶质标记物的抗体进行双重免疫染色。在正常对照脑中，14-3-3免疫反应主要定位于神经元胞体和突起，一些胶质细胞仅显示弱免疫反应。在MS患者斑块病变中，星形胶质细胞和少突胶质细胞呈强免疫反应性，一些小胶质细胞和巨噬细胞也呈强免疫反应性，其中大多数位于血管周围区域。在PML脑中，在脱髓鞘病变中观察到类似的免疫标记模式，其中星形胶质细胞和少突胶质细胞表现出密集的14-3-3免疫反应性。我们的研究结果表明，14-3-3可能是上调的胶质细胞，特别是星形胶质细胞和少突胶质细胞，在MS或PML患者。夸张的14-3-3在这些神经胶质细胞中的积累可能与这两种脱髓鞘疾病的发病机制有关。
14-3-3 proteins have been shown to be increased in the cerebrospinal fluid from patients with several kinds of neurological diseases, including multiple sclerosis (MS). To investigate whether 14-3-3 proteins are closely related to the pathogenesis of MS, we performed immunohistochemical studies for 14-3-3 in autopsied brains from ten patients with MS, five patients with progressive multifocal leukoencephalopathy (PML), and seven normal control subjects. Formalin-fixed, paraffin-embedded sections from all cases were immunostained with a specific anti-14-3-3 antibody, and some sections from the MS cases were double-immunostained with antibodies raised against 14-3-3 and glial markers. In the normal control brains, 14-3-3 immunoreactivity was localized mainly in the neuronal somata and processes, and some glial cells showed only weak immunoreactivity. In the plaque lesions from the MS cases, the astrocytes and oligodendrocytes were intensely immunostained, and strong immunoreactivity was also found in some microglia and macrophages, most of which were located in the perivascular areas. In the PML brains, a similar immunolabeling pattern was observed in the demyelinated lesions, in which the astrocytes and oligodendrocytes exhibited dense 14-3-3 immunoreactivity. Our results suggest that 14-3-3 may be up-regulated in the glial cells, especially in astrocytes and oligodendrocytes, in patients with MS or PML. The exaggerated 14-3-3 accumulation in these glial elements may be associated with the pathogenesis of both demyelinating disorders.