Istrin Gili, Bosis Eran, Solomon Beka
Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
J Neurosci Res. 2006 Aug 1;84(2):434-43. doi: 10.1002/jnr.20886.
Intravenous immunoglobulin (IVIg), a purified immunoglobulin fraction manufactured from the blood of healthy humans, is an FDA-approved treatment for many immune and inflammatory diseases. Recent studies have demonstrated that IVIg therapy has several positive effects on patients with Alzheimer's disease (AD). These include improving cognitive functions and lowering the level of soluble amyloid-beta peptide (AbetaP) in the brain. Nonetheless, the mechanism by which IVIg mediates the clearance of AbetaP from the AD brain currently remains unknown. In this study we investigated the molecular basis for the direct and indirect effects of IVIg on AbetaP clearance using the BV-2 cellular microglia line. Specifically, we show that IVIg dissolves preformed AbetaP fibrils in vitro. Moreover, IVIg increases cellular tolerance to AbetaP, enhances microglial migration toward AbetaP deposits, and mediates phagocytosis of AbetaP. Thus, several mechanisms can be considered when examining the effects of IVIg. Our work supports the hypothesis that IVIg interferes by more than one mechanism in clearing AbetaP from the brains of Alzheimer's patients.
静脉注射免疫球蛋白（IVIg）是一种从健康人血液中提取的纯化免疫球蛋白组分，是一种经美国食品药品监督管理局（FDA）批准用于治疗多种免疫和炎症性疾病的药物。最近的研究表明，IVIg疗法对阿尔茨海默病（AD）患者有多种积极作用。这些作用包括改善认知功能以及降低大脑中可溶性淀粉样β肽（AbetaP）的水平。尽管如此，IVIg介导从AD大脑中清除AbetaP的机制目前仍不清楚。在本研究中，我们使用BV-2小胶质细胞系研究了IVIg对AbetaP清除的直接和间接作用的分子基础。具体而言，我们发现IVIg在体外可溶解预先形成的AbetaP纤维。此外，IVIg可提高细胞对AbetaP的耐受性，增强小胶质细胞向AbetaP沉积物的迁移，并介导对AbetaP的吞噬作用。因此，在研究IVIg的作用时可以考虑多种机制。我们的工作支持这样一种假说，即IVIg通过多种机制干扰从阿尔茨海默病患者大脑中清除AbetaP的过程。
