Yin Guo Nan, Jeon Hyejin, Lee Shinrye, Lee Ho Won, Cho Je-Yoel, Suk Kyoungho
Department of Pharmacology, Brain Science and Engineering Institute, CMRI, Kyungpook National University School of Medicine, Daegu, Korea.
J Neurosci Res. 2009 Aug 15;87(11):2578-90. doi: 10.1002/jnr.22081.
Proteomic analysis of cerebrospinal fluid (CSF) samples derived from patients with Alzheimer's disease (AD) or Parkinson's disease (PD) was performed. On the basis of liquid chromatography-tandem mass spectrometry, two-dimensional gel electrophoresis analysis, and Western blot validation, it was found that the level of soluble form of monocyte differentiation antigen CD14 precursor was elevated in CSF from AD or PD patients compared with normal subjects. The soluble CD14 protein and mRNA expression was detected in microglia cells, indicating that microglia may be a cellular source of soluble CD14 in CSF. Next, the role of soluble CD14 in the regulation of glial functions was investigated. Soluble CD14 inhibited lipopolysaccharide (LPS)- or LPS/interferon-gamma-induced nitric oxide production and cell death of microglia and astrocytes. Soluble CD14 suppressed glial neurotoxicity in a coculture of glia/neuroblastoma. In addition, soluble CD14 moderately enhanced phagocytic activity of microglia. These results suggest that microglia-derived soluble CD14 is a candidate CSF biomarker for AD and PD, and the soluble CD14 may inhibit glial activation by interfering with LPS effects.
对来自阿尔茨海默病（AD）或帕金森病（PD）患者的脑脊液（CSF）样本进行了蛋白质组学分析。基于液相色谱 - 串联质谱、二维凝胶电泳分析和蛋白质印迹验证，发现与正常受试者相比，AD或PD患者脑脊液中单核细胞分化抗原CD14前体的可溶性形式水平升高。在小胶质细胞中检测到可溶性CD14蛋白和mRNA表达，表明小胶质细胞可能是脑脊液中可溶性CD14的细胞来源。接下来，研究了可溶性CD14在调节神经胶质细胞功能中的作用。可溶性CD14抑制脂多糖（LPS）或LPS/干扰素 - γ诱导的小胶质细胞和星形胶质细胞的一氧化氮产生和细胞死亡。可溶性CD14在神经胶质细胞/神经母细胞瘤共培养中抑制神经胶质细胞神经毒性。此外，可溶性CD14适度增强小胶质细胞的吞噬活性。这些结果表明，小胶质细胞衍生的可溶性CD14是AD和PD的脑脊液生物标志物候选物，并且可溶性CD14可能通过干扰LPS作用来抑制神经胶质细胞活化。
