Lipopolysaccharide affects Golli expression and promotes proliferation of oligodendrocyte progenitors
Lipopolysaccharide affects Golli expression and promotes proliferation of oligodendrocyte progenitors
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DOI：
10.1002/glia.20125
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发表时间：
2005-03-01
期刊：
影响因子：
6.2
通讯作者：
Zecevic, N
中科院分区：
文献类型：
--
作者：
Filipovic, R;Zecevic, N
少突胶质细胞祖细胞（OPCs）的增殖对脱髓鞘疾病的初始髓鞘形成和再髓鞘形成至关重要。先前，我们发现在多发性硬化症病变周围存在大量的OPCs和活化的小胶质细胞，并且它们积累Golli蛋白。胶质蛋白存在于神经元和免疫细胞中，可能在免疫过程中以及神经元和少突胶质细胞的发育中发挥作用。我们假设小胶质细胞在炎症反应中产生的Golli蛋白促进了OPCs的增殖。为了验证这一假设，我们用细菌内毒素脂多糖（LPS）在新生小鼠脑切片培养中诱导炎症。处理后的切片显示OPCs数量增加。一些结果支持LPS的这种作用是通过激活小胶质细胞和上调Golli蛋白来传递的观点。首先，免疫荧光和Western blot分析显示，lps处理的脑切片中Golli蛋白的表达增加。其次，Golli蛋白仅在lps处理的小胶质细胞培养物（LPS-MCM）的条件培养基中存在，而在lps处理的星形胶质细胞的条件培养基或对照培养基中均不存在。第三，LPS- mcm或Golli蛋白能促进纯化的OPCs的增殖，而单独LPS则不能。综上所述，这些结果表明，小胶质细胞和/或小胶质细胞分泌因子对于lps促进的OPCs增殖是必要的，并提示Golli蛋白可能作为一种介质参与了这一过程。(C) 2004 Wiley-Liss, Inc。
Proliferation of oligodendrocyte progenitor cells (OPCs) is important for initial myelination as well as for remyelination in demyelinating diseases. Previously, we showed that numerous OPCs and activated microglia, are present around multiple sclerosis lesions, and that they accumulate Golli proteins. Golli proteins, present in both neuronal and immune cells, might have a role in the immune processes, as well as in development of neurons and oligodendrocytes. We hypothesize that Golli proteins, generated by microglia in response to inflammation, promote proliferation of OPCs. To test this hypothesis, we induced inflammation in neonatal mouse brain slice culture with bacterial endotoxin lipopolysaccharide (LPS). Treated slices showed an increase in the number of OPCs. Several results support the notion that this effect of LPS is conveyed through activation of microglia and upregulation of Golli proteins. First, LPS-treated brain slices have increased expression of Golli proteins observed by immunofluorescence and Western blot analysis. Second, Golli proteins were demonstrated only in the conditioned medium from LPS-treated microglial cell cultures (LPS-MCM), and were absent in either the conditioned media from LPS-treated astrocytes or the control media. Third, proliferation of purified OPCs was promoted with LPS-MCM or Golli proteins, but not with LPS alone. Taken together, these results demonstrate that microglia and/or microglia secreted factors, are necessary for the LPS-promoted proliferation of OPCs and suggest possible involvement of Golli proteins as one of mediators in this process. (C) 2004 Wiley-Liss, Inc.