期刊
EXPERIMENTAL NEUROLOGY
卷 171, 期 1, 页码 29-45出版社
ACADEMIC PRESS INC
DOI: 10.1006/exnr.2001.7732
关键词
inflammation; Alzheimer's disease; microglia; amyloid beta-peptide; macrophage colony stimulating factor; chemotaxis; gene expression; neurons; activation; human glial culture
资金
- NHLBI NIH HHS [HL60901, HL56881] Funding Source: Medline
- NIA NIH HHS [AG14103, AG00690, AG16736, AG07367] Funding Source: Medline
Receptor-mediated interactions with amyloid beta -peptide (A beta) could be important in the evolution of the inflammatory. processes and cellular dysfunction that are prominent in Alzheimer's disease (AD) pathology. One candidate receptor is the receptor for advanced glycation endproducts (RAGE), which can bind A beta and transduce signals leading to cellular activation. Data are presented showing a potential mechanism for A beta activation of microglia that could be mediated by RAGE and macrophage colony-stimulating factor (M-CSF). Using brain tissue from AD and nondemented (ND) individuals, RAGE expression was shown to be present on microglia and neurons of the hippocampus, entorhinal cortex, and superior frontal gyrus. The presence of increased numbers of RAGE-immunoreactive microglia in AD led us to further analyze RAGE-related properties of these cells cultured from AD and ND brains. Direct addition of A beta (1-42) to the microglia increased their expression of M-CSF. This effect was significantly greater in microglia derived from AD brains compared to those from ND brains. Increased M-CSF secretion was also demonstrated using a cell culture model of plaques whereby microglia were cultured in wells containing focal deposits of immobilized A beta (1-42). In each case, the A beta stimulation of M-CSF secretion was significantly blocked by treatment of cultures with anti-RAGE F(ab ')(2). Treatment of microglia with anti-RAGE F(ab ')(2), also inhibited the chemotactic response of microglia toward A beta (1-42). Finally, incubation of microglia with M-CSF and A beta increased expression of RAGE mRNA. These microglia also expressed M-CSF receptor mRNA. These data suggest a positive feedback loop in which A beta -RAGE-mediated microglial activation enhances expression of M-CSF and RAGE, possibly initiating an ascending spiral of cellular activation. (C) 2001 Academic Press.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据