Chemokines regulate the migration of neural progenitors to sites of neuroinflammation
Chemokines regulate the migration of neural progenitors to sites of neuroinflammation
复制标题
DOI：
10.1523/jneurosci.0156-06.2006
复制
发表时间：
2006-03-22
影响因子：
5.3
通讯作者：
Miller, RJ
中科院分区：
文献类型：
--
作者：
Belmadani, A;Tran, PB;Miller, RJ
许多研究表明，移植或内源性神经前体细胞将迁移到大脑的受损区域。然而，这种影响的机制尚不清楚。在这里，我们报告说，使用海马切片培养，移植的神经祖细胞（NP）迁移到神经炎症的地区，趋化因子是这一过程的主要调节剂。将炎症刺激物注射到海马伞区域并将增强型绿色荧光蛋白（EGFP）标记的NPs移植到培养的海马脑片的齿状回中后，观察NPs的迁移。移植后3 ~ 7 d，对照组脑片中的EGFP-NPs几乎没有迁移倾向，并已分化为神经元和胶质细胞。相反，在注射炎症刺激物的切片中，EGFP-NPs向注射部位迁移.这些切片中的NP也存活得不太好。使用的炎症刺激物是细胞因子肿瘤坏死因子-α和干扰素-γ、细菌毒素脂多糖、人类免疫缺陷病毒-1外壳蛋白糖蛋白120或表达β-淀粉样蛋白的腺病毒的组合。我们发现，这些炎症刺激增加了海马脑片的许多趋化因子和细胞因子的合成。当将来自CC趋化因子受体CCR 2敲除小鼠的EGFP-NP移植到切片中时，它们几乎没有向炎症部位迁移。类似地，当移植到由单核细胞趋化蛋白-1（MCP-1）敲除小鼠制备的切片中时，野生型EGFP-NP几乎没有向炎症部位迁移。这些数据表明，神经炎症部位分泌的因子对神经祖细胞有吸引力，并表明趋化因子如MCP-1在此过程中发挥重要作用。
Many studies have shown that transplanted or endogenous neural progenitor cells will migrate toward damaged areas of the brain. However, the mechanism underlying this effect is not clear. Here we report that, using hippocampal slice cultures, grafted neural progenitor cells (NPs) migrate toward areas of neuroinflammation and that chemokines are a major regulator of this process. Migration of NPs was observed after injecting an inflammatory stimulus into the area of the fimbria and transplanting enhanced green fluorescent protein (EGFP)- labeled NPs into the dentate gyrus of cultured hippocampal slices. Three to 7 d after transplantation, EGFP - NPs in control slices showed little tendency to migrate and had differentiated into neurons and glia. In contrast, in slices injected with inflammatory stimuli, EGFP - NPs migrated toward the site of the injection. NPs in these slices also survived less well. The inflammatory stimuli used were a combination of the cytokines tumor necrosis factor-alpha and interferon-gamma, the bacterial toxin lipopolysaccharide, the human immunodeficiency virus-1 coat protein glycoprotein 120, or a beta-amyloid-expressing adenovirus. We showed that these inflammatory stimuli increased the synthesis of numerous chemokines and cytokines by hippocampal slices. When EGFP - NPs from CC chemokine receptor CCR2 knock-out mice were transplanted into slices, they exhibited little migration toward sites of inflammation. Similarly, wild-type EGFP - NPs exhibited little migration toward inflammatory sites when transplanted into slices prepared from monocyte chemoattractant protein-1 (MCP-1) knock-out mice. These data indicate that factors secreted by sites of neuroinflammation are attractive to neural progenitors and suggest that chemokines such as MCP-1 play an important role in this process.