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首页> 外文期刊>The European Journal of Neuroscience >Significant higher-level C-C motif chemokine ligand 2/3 and chemotactic power in cerebral white matter than grey matter in rat and human
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Significant higher-level C-C motif chemokine ligand 2/3 and chemotactic power in cerebral white matter than grey matter in rat and human

机译：显着的高级C-C主题趋化因子配体2/3和脑白质的趋化力，比大鼠和人类灰质

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Recent observations indicate that cerebral white matter (WM) exhibits a higher che-moattractant capability for immune cells. The C-C motif chemokine ligands 2 and 3 (CCL2, CCL3) are key chemokines for monocytes and T cells. However, tissue differential of these chemokines is unclear, although the higher CCL2/3 mRNA levels were found in rodent WM. It has been shown that more immune cells infiltrated to WM than to grey matter (GM) in multiple sclerosis (MS) and human/simian immunodeficiency virus (HIV/SIV)-infected brains. More nodular lesions have also been identified in the WM of patients with MS or HIV/SIV encephalitis. We hypothesize that higher levels of CCL2/3 in the WM may associate with neuropathogenesis. To test this hypothesis, we compared CCL2 and CCL3 peptide levels in WM and GM of rat and human, and found both were significantly higher in the WM. Next, we tested the effect of CCL2 on primary rat microglia migration and observed a dose-dependent migratory pattern. Then, we assessed effects of WM and GM homogen-ates on microglia chemotaxis and observed significant stronger effects of WM than GM in a concentration-dependent manner. The concentration-dependent pattern of tissue homogenates on chemotaxis was similar to the effect of CCL2. Finally, we found the chemoattractant effects of WM on microglia were significantly attenuated by addition of a CCL2 receptor blocker to culture medium and a neutralizing antibody against CCL3 functional motif in the WM homogenate. Taking together, these results suggest that CCL2/3 played significant roles in the microglia chemotaxis toward WM homogenate.
机译：最近的观察表明，大脑白质（WM）对免疫细胞具有更高的吞噬能力。C-C基序趋化因子配体2和3（CCL2，CCL3）是单核细胞和T细胞的关键趋化因子。然而，这些趋化因子的组织差异尚不清楚，尽管在啮齿类动物WM中发现了较高的CCL2/3 mRNA水平。研究表明，在多发性硬化症（MS）和人类免疫缺陷病毒（HIV/SIV）感染的大脑中，向WM浸润的免疫细胞多于向灰质（GM）浸润的免疫细胞。在MS或HIV/SIV脑炎患者的WM中也发现了更多结节性病变。我们假设西医治疗中较高水平的CCL2/3可能与神经病变有关。为了验证这一假设，我们比较了大鼠和人的西医和GM中CCL2和CCL3肽的水平，发现两者在西医中都显著较高。接下来，我们测试了CCL2对原代大鼠小胶质细胞迁移的影响，并观察到剂量依赖性迁移模式。然后，我们评估了WM和GM同源ATE对小胶质细胞趋化性的影响，并观察到WM的作用明显强于GM，且呈浓度依赖性。组织匀浆对趋化性的浓度依赖模式与CCL2的作用相似。最后，我们发现，通过在培养基中添加CCL2受体阻滞剂和WM匀浆中针对CCL3功能基序的中和抗体，WM对小胶质细胞的化学吸引作用显著减弱。综上所述，这些结果表明CCL2/3在小胶质细胞对WM匀浆的趋化性中发挥了重要作用。

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