Inflammatory repertoire of Alzheimer's disease and nondemented elderly microglia in vitro

被引:328
作者
Lue, LF
Rydel, R
Brigham, EF
Yang, LB
Hampel, H
Murphy, GM
Brachova, L
Yan, SD
Walker, DG
Shen, Y
Rogers, J
机构
[1] Sun Hlth Res Inst, Sun City, AZ 85372 USA
[2] Elan Pharmaceut, San Francisco, CA USA
[3] Univ Munich, Dept Psychiat, Dementia Res Sect, D-8000 Munich, Germany
[4] Univ Munich, Memory Clin, D-8000 Munich, Germany
[5] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Neurosci Res Labs, Stanford, CA 94305 USA
[6] Columbia Univ, Dept Pathol, New York, NY USA
关键词
glia; cell culture; Alzheimer's disease; cytokines; chemokines; complement; inflammation;
D O I
10.1002/glia.1072
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We have previously developed and characterized isolated microglia and astrocyte cultures from rapid (<4 h) brain autopsies of Alzheimer's disease (AD) and nondemented elderly control (ND) patients. In the present study, we evaluate the inflammatory repertoire of AD and ND microglia cultured from white matter (corpus callosum) and gray matter (superior frontal gyrus) with respect to three major proinflammatory cytokines, three chemokines, a classical pathway complement component, a scavenger cell growth factor, and a reactive nitrogen intermediate. Significant, dose-dependent increases in the production of pro-interleukin-1<beta> (pro-IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory peptide-1 alpha (MIP-1 alpha), IL-8, and macrophage colony-stimulating factor (M-CSF) were observed after exposure to pre-aggregated amyloid beta peptide (1-42) (A beta1-42). Across constitutive and A beta -stimulated conditions, secretion of complement component C1q, a reactive nitrogen intermediate, and M-CSF was significantly higher in AD compared with ND microglia. Taken together with previous in situ hybridization findings, these results demonstrate unequivocally that elderly human microglia provide a brain endogenous source for a wide range of inflammatory mediators. GLIA 35:72-79, 2001. (C) 2001 Wiley-Liss, Inc.
引用
收藏
页码:72 / 79
页数:8
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