INTERLEUKIN-6 AND ALPHA-2-MACROGLOBULIN INDICATE AN ACUTE-PHASE STATE IN ALZHEIMERS-DISEASE CORTICES
INTERLEUKIN-6 AND ALPHA-2-MACROGLOBULIN INDICATE AN ACUTE-PHASE STATE IN ALZHEIMERS-DISEASE CORTICES
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DOI：
10.1016/0014-5793(91)80737-n
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发表时间：
1991-07-08
期刊：
影响因子：
3.5
通讯作者：
BERGER, M
中科院分区：
文献类型：
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作者：
BAUER, J;STRAUSS, S;BERGER, M
最近的研究表明，阿尔茨海默病（AD）老年斑的主要成分β - a4肽的形成不是由其前体淀粉样前体蛋白（APP）的正常加工引起的。由于发现APP在其β - a4序列内的蛋白水解裂解是APP加工的一部分，因此在正常条件下，β - a4肽的形成似乎被阻止。我们考虑了一种内源性蛋白酶抑制剂是否会干扰AD的APP加工。在我们最近发现培养的人类神经元细胞在炎症介质白细胞介素-6 （IL-6）的刺激下合成已知的最有效的人类蛋白酶抑制剂α -2-巨球蛋白（α - 2m）之后，我们现在研究α - 2m和IL-6是否可以在AD大脑中检测到。在这里，我们报道阿尔茨海默病皮层老年斑显示出强烈的α - 2m和IL-6免疫反应性，而在年龄匹配的对照大脑中没有发现这种免疫反应性。阿尔茨海默病脑组织海马CA1神经元核周α - 2m免疫反应性强，表明神经元细胞是阿尔茨海默病脑组织α - 2m合成的部位。我们未发现AD患者脑脊液中IL-6或α - 2m水平升高。我们的数据表明，一系列似乎局限于局部皮层环境的免疫事件是AD病理的一部分。
Recent studies indicated that the formation of a major constituent of Alzheimer's disease (AD) senile plaques, called beta-A4-peptide, does not result from normal processing of its precursor, amyloid precursor protein (APP). Since proteolytic cleavage of APP inside its beta-A4 sequence was found to be part of APP processing the formation of the beta-A4-peptide seems to be prevented under normal conditions. We considered whether in AD one of the endogenous proteinase inhibitors might interfere with APP processing. After we had recently found that cultured human neuronal cells synthesize the most potent of the known human proteinase inhibitors, alpha-2-macroglobulin (alpha-2M), upon stimulation with the inflammatory mediator interleukin-6 (IL-6) we now investigated whether alpha-2M and IL-6 could be detected in AD brains. Here we report that AD cortical senile plaques display strong alpha-2M and IL-6 immunoreactivity while no such immunoreactivity was found in age-matched control brains. Strong perinuclear alpha-2M immunoreactivity in hippocampal CA1 neurons of Alzheimer's disease brains indicates that neuronal cells are the site of alpha-2M synthesis in AD brains. We did not detect elevated IL-6 or alpha-2M levels in the cerebrospinal fluid of AD patients. Our data indicate that a sequence of immunological events which seem to be restricted to the local cortical environment is part of AD pathology.