Strauss S, Bauer J, Ganter U, Jonas U, Berger M, Volk B
Abteilung Neuropathologie, Universität Freiburg, Germany.
Lab Invest. 1992 Feb;66(2):223-30.
We examined brains from Alzheimer's disease (AD) patients by immunohistochemistry for the presence of protease inhibitors. Immunoreactivity for alpha 2-macroglobulin (alpha 2-M), the most potent of the known human protease inhibitors, was found in a subgroup of cortical and hippocampal AD senile plaques. In addition, large hippocampal neurons in AD brains displayed intracellular alpha 2-M immunoreactivity which was consistently stronger than in normal aged brains. In cultured human cells of neurogenic origin (SH-SY5Y neuroblastoma cells), alpha 2-M synthesis could be strongly induced by the inflammatory cytokine interleukin-6 (IL-6) indicating that human alpha 2-M behaves as an acute-phase protein in the nervous system. Therefore, we also examined AD brains for the presence of IL-6 and found strong immunostaining in and around a subgroup of senile plaques as well as around large cortical neurons. Only very few senile plaques also stained for C-reactive protein, an acute phase protein known to be inducible by IL-6. We propose that the presence of IL-6 and alpha 2-M immunoreactivity in AD brains is functionally linked and that a sequence of immunological events is part of the pathology of AD.
我们通过免疫组织化学检查了阿尔茨海默病（AD）患者的大脑，以检测蛋白酶抑制剂的存在。在已知的人类蛋白酶抑制剂中效力最强的α2-巨球蛋白（α2-M），在皮质和海马区AD老年斑的一个亚组中发现有免疫反应性。此外，AD大脑中的大型海马神经元显示出细胞内α2-M免疫反应性，且始终比正常老年大脑中的更强。在神经源性的培养人类细胞（SH-SY5Y神经母细胞瘤细胞）中，炎症细胞因子白细胞介素-6（IL-6）可强烈诱导α2-M的合成，这表明人类α2-M在神经系统中表现为一种急性期蛋白。因此，我们还检查了AD大脑中IL-6的存在情况，发现在老年斑的一个亚组内部及其周围以及大型皮质神经元周围有强烈的免疫染色。只有极少数老年斑也对C反应蛋白染色，C反应蛋白是一种已知可被IL-6诱导的急性期蛋白。我们提出，AD大脑中IL-6和α2-M免疫反应性的存在存在功能联系，并且一系列免疫事件是AD病理学的一部分。
