Kopec K K, Carroll R T
Department of Neuroscience Therapeutics, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert, Ann Arbor, Michigan 48105, USA.
J Neurochem. 1998 Nov;71(5):2123-31. doi: 10.1046/j.1471-4159.1998.71052123.x.
Beta-amyloid (A beta) peptides are a key component of the senile plaques that characterize Alzheimer's disease. Cytokine-producing microglia have been shown to be intimately associated with amyloid deposits and have also been implicated as scavengers responsible for clearing A beta deposits. However, little is known about the initial activation of these microglia or the effect of A beta on phagocytosis. Murine BV-2 microglia were used to assess the effect of synthetic A beta 1-42 on phagocytosis by quantifying uptake of fluorescent microspheres, acetylated low-density lipoproteins, and zymosan particles by flow cytometry. A beta 1-42 stimulated microglial phagocytosis in a time- and dose-dependent manner. A beta fibrils produced the greatest potentiation, and once activated, phagocytosis remained elevated after removal of A beta from the cultures. A beta-stimulated phagocytosis could be blocked if proteoglycans were first complexed to A beta fibrils. These data suggest that A beta fibrils act as an immune signal to stimulate microglial phagocytosis and that extracellular matrix molecules may modify A beta function.
β-淀粉样蛋白（Aβ）肽是构成阿尔茨海默病特征性老年斑的关键成分。已证明产生细胞因子的小胶质细胞与淀粉样沉积物密切相关，并且也被认为是负责清除Aβ沉积物的清道夫。然而，关于这些小胶质细胞的初始激活或Aβ对吞噬作用的影响知之甚少。通过流式细胞术对荧光微球、乙酰化低密度脂蛋白和酵母聚糖颗粒的摄取进行定量，使用小鼠BV-2小胶质细胞来评估合成Aβ1-42对吞噬作用的影响。Aβ1-42以时间和剂量依赖性方式刺激小胶质细胞吞噬作用。Aβ原纤维产生最大的增强作用，并且一旦被激活，从培养物中去除Aβ后吞噬作用仍保持升高。如果蛋白聚糖首先与Aβ原纤维复合，则Aβ刺激的吞噬作用可能被阻断。这些数据表明，Aβ原纤维作为一种免疫信号来刺激小胶质细胞吞噬作用，并且细胞外基质分子可能会改变Aβ的功能。
