Interaction between microglia and oligodendrocyte cell progenitors involves Golli proteins
Interaction between microglia and oligodendrocyte cell progenitors involves Golli proteins
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DOI：
10.1196/annals.1342.015
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Zecevic, N
中科院分区：
文献类型：
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作者：
Filipovic, R;Zecevic, N
多发性硬化症(MS)是一种自身免疫性慢性炎症性疾病，以中枢神经系统内斑块、髓鞘破坏为特征，导致患者多种残疾。除脱髓鞘斑块外，病理生理学研究还显示了代表部分髓鞘再生区域的“影子斑块”。新的髓鞘可以由少突胶质细胞(OL)产生，这些少突胶质细胞祖细胞(OPC)预先存在于脱髓鞘区域或从周围区域招募。为了成功地重建脱髓鞘区域，OPC必须增殖、迁移并分化为能够形成髓鞘的成熟OL。确定影响再髓鞘形成的因素是发育神经生物学的当前课题。此前，我们发现在神经系统和免疫系统中广泛分布的Golli蛋白存在于OPC和MS病变周围激活的小胶质细胞中。我们推测，在炎症反应中，Golli蛋白可能通过小胶质细胞促进OPC的增殖。为了测试这一点，我们建立了新生小鼠脑片和细胞培养，并使用脂多糖(LPS)来诱导炎症。在内毒素处理的脑片中，Golli蛋白在皮质脑室下区表达增加。此外，只有经内毒素处理的小胶质细胞培养的条件培养液(LPS-MCM)中才有Golli蛋白的表达，而在经内毒素处理的星形胶质细胞的条件培养液和对照培养液中均不表达Golli蛋白。LPS-MCM或GALLI蛋白可促进纯化的OPC的增殖，但不能单独作用于LPS。综上所述，这些结果表明激活的小胶质细胞有利于OPC的增殖，并提示Golli蛋白可能参与了这一过程。
Multiple sclerosis (MS) is an autoimmune and chronic inflammatory disease characterized by plaques, areas of destroyed myelin sheaths in the CNS, which results in multiple disabilities for patients. In addition to demyelinated plaques, pathophysiological studies have shown "shadow plaques" that represent areas of partial remyelination. New myelin can be made by oligodendrocytes (OLs) generated from oligodendrocyte progenitor cells (OPCs) that pre-exist in the demyelinated area or recruited from surrounding areas. To successfully repopulate the demyelinated area, OPCs have to proliferate, migrate, and differentiate into mature OLs capable of forming myelin. Identifying factors that influence remyelination is a current topic in developmental neurobiology. Previously, we showed that Golli proteins, which have a broad distribution in the nervous and immune systems, are present both in OPCs and activated microglia around MS lesions. We hypothesized that in response to inflammation, Golli proteins may promote proliferation of OPCs through microglial cells. To test this, we established neonatal mouse brain slice and cell cultures and used lipopolysaccharide (LPS) to induce inflammation. In LPS-treated brain slices, Golli proteins displayed increased expression in the cortical subventricular zone. Furthermore, Golli proteins were demonstrated only in the conditioned medium from LPS-treated microglial cell cultures (LPS-MCM), and were absent in either conditioned medium from LPS-treated astrocytes or control media. Finally, proliferation of purified OPCs was promoted with LPS-MCM or Golli proteins, but not with LPS alone. In summary, these results demonstrate that activated microglia are beneficial for proliferation of OPCs and suggest possible involvement of Golli proteins as one of mediators in this process.