Role of soluble CD14 in cerebrospinal fluid as a regulator of glial functions.
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.
Yin
Guo Nan
GN
Department of Pharmacology, Brain Science and Engineering Institute, CMRI, Kyungpook National University School of Medicine, Daegu, Korea.
Jeon
Hyejin
H
Lee
Shinrye
S
Lee
Ho Won
HW
Cho
Je-Yoel
JY
Suk
Kyoungho
K
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D000818:Animals; D001253:Astrocytes / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D002460:Cell Line; D018920:Coculture Techniques; D006801:Humans; D007371:Interferon-gamma / Q000633:toxicity; D018950:Lipopolysaccharide Receptors / Q000134:cerebrospinal fluid* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D017628:Microglia / Q000502:physiology; D008875:Middle Aged; D009447:Neuroblastoma / Q000503:physiopathology; D009457:Neuroglia / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D010300:Parkinson Disease / Q000134:cerebrospinal fluid*; D010587:Phagocytosis / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism
D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D009569:Nitric Oxide; D007371:Interferon-gamma