AMYLOID PRECURSOR PROTEIN (APP) EXPRESSION IN MULTIPLE-SCLEROSIS LESIONS
AMYLOID PRECURSOR PROTEIN (APP) EXPRESSION IN MULTIPLE-SCLEROSIS LESIONS
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DOI：
10.1002/glia.440150206
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发表时间：
1995-10-01
期刊：
影响因子：
6.2
通讯作者：
NEWCOMBE, J
中科院分区：
文献类型：
--
作者：
GEHRMANN, J;BANATI, RB;NEWCOMBE, J
淀粉样前体蛋白（APP）在反应性胶质细胞中响应于包括炎症在内的多种病理刺激而被快速诱导。在本研究中，以前在自身免疫性中枢神经系统炎症动物模型中进行的观察已扩展到多发性硬化（MS）病变的分析。共30个新鲜冷冻组织块从6个组织病理学正常的对照和6个MS病例已检查免疫细胞化学与单克隆抗体针对任何C-或N-末端表位的APP。组织学评价疾病进展的基础上苏木精-伊红和油红O染色和免疫细胞化学的T细胞，巨噬细胞/小胶质细胞，星形胶质细胞和少突胶质细胞。在对照组中，APP免疫反应性普遍较低，仅限于血管壁、白色的少突胶质细胞和灰质中的神经元。然而，在活跃的脱髓鞘斑块中，APP免疫反应性水平很高，定位于T淋巴细胞、泡沫状巨噬细胞、活化的小胶质细胞和反应性星形胶质细胞，包括星形胶质细胞过程。在慢性病变中，APP免疫反应性水平通常低于急性病变，主要见于反应性星形胶质细胞、其过程和少数巨噬细胞/小胶质细胞，这取决于斑块发展的阶段。此外，一些14 E阳性少突胶质细胞，而且，许多轴突表现出APP免疫反应性，这是特别明显的抗C-末端抗体。这些结果表明，APP诱导反应性神经胶质细胞，但也对T淋巴细胞脱髓鞘过程中。APP表达的程度似乎与组织病理学病变发展相关，因此表明APP检测可作为MS疾病进展的敏感标志物。（C）1995 Wiley-Liss，Inc.
The amyloid precursor protein (APP) is rapidly induced in reactive glial cells in response to several pathological stimuli including inflammation. In the present study, observations previously made in animal models of autoimmune central nervous system inflammation have been extended to the analysis of multiple sclerosis (MS) lesions. A total of thirty fresh-frozen tissue blocks from six histopathologically normal control and six MS eases have been examined immunocytochemically with monoclonal antibodies directed against either C- or N-terminal epitopes of APP. Histopathological evaluation of disease progression was based on hematoxylin-eosin and oil red O staining and immunocytochemistry for T cells, macrophages/microglia, astrocytes, and oligodendrocytes. In control cases, APP immunoreactivity was generally low and confined to blood vessel walls, oligodendrocytes in white, and neurons in grey matter. In actively demyelinating plaques, however, levels of APP immunoreactivity were high, localised on T lymphocytes, foamy macrophages, activated microglia, and reactive astrocytes including astrocytic processes. In more chronic lesions, levels of APP immunoreactivity were generally lower than in acute lesions, mainly found on reactive astrocytes, their processes and a few macrophages/microglia depending on the stage of plaque development. In addition, a few 14E-positive oligodendrocytes and, moreover, numerous axons exhibited APP immunoreactivity, which was particularly pronounced with anti-C-terminal antibodies. These results demonstrate that APP is induced on reactive glial cells but also on T lymphocytes during demyelination. The extent of APP expression appears to be correlated to histopathological lesion development and thus suggests that APP detection serves as a sensitive marker for disease progression in MS. (C) 1995 Wiley-Liss, Inc.