Regulation of chemokine receptor expression in human microglia and astrocytes

Regulation of chemokine receptor expression in human microglia and astrocytes
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DOI:
10.1016/s0165-5728(03)00009-2
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发表时间:
2003-03-01
影响因子:
3.3
通讯作者:
Male, D
Male, D
中科院分区:
医学4区
文献类型:
--
作者:
Flynn, G;Maru, S;Male, D

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已经有人提出,移动细胞在组织中的位置由它们的趋化因子受体的整体特征决定。这项研究检测了静止和激活的成人小胶质细胞、星形胶质细胞和小胶质细胞系CHME3上表达的趋化因子受体的分布。小胶质细胞表达最高水平的CXCR1、CXCR3和CCR3。星形胶质细胞也有中等水平的CXCR1和CXCR3,以及一些CCR3,两种类型的细胞也都低水平表达CCR4、CCR5、CCR6、CXCR2、CXCR4和CXCR5。在炎性细胞因子肿瘤坏死因子-α(TNFpha)和干扰素-γ(IFNGamma)作用下,细胞在24小时内部分但不是全部受体的表达增加。小胶质细胞对受体的表达有中等程度的增强,而星形胶质细胞对肿瘤坏死因子α的反应尤其强烈,CXCR3、CCR3和CXCR1增强。然而,小胶质细胞和星形胶质细胞对同一趋化因子的迁移和增殖反应是不同的,小胶质细胞迁移和星形胶质细胞增殖是CXCL10的反应。这些数据表明,在中枢神经系统疾病过程中,激活的小胶质细胞和星形胶质细胞对炎性趋化因子变得选择性更敏感的机制,本文讨论了中枢神经系统中存在的众多趋化因子中的哪一种对小胶质细胞和星形胶质细胞具有优先作用。(C)2003 Elsevier Science B.V.保留所有权利。
It has been proposed that the positioning of mobile cells within a tissue is determined by their overall profile of chemokine receptors. This study examines the profiles of chemokine receptors expressed on resting and activated adult human microglial cells, astrocytes and a microglial cell line, CHME3. Microglia express highest levels of CXCR1, CXCR3 and CCR3. Astrocytes also have moderate levels of CXCR1 and CXCR3, and some CCR3, while both cell types also expressed CCR4, CCR5, CCR6, CXCR2, CXCR4 and CXCR5 at lower levels. Activation of the cells with the inflammatory cytokine tumour necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma) increased the expression of some but not all receptors over a period of 24 h. Microglia showed moderate enhancement of receptor expression, while astrocytes responded particularly strongly to TNFalpha with enhanced CXCR3, CCR3 and CXCR1. However, the migratory and proliferative responses of the microglia and astrocytes to the same chemokine were different, with microglia migrating and astrocytes proliferating in response to CXCL10. The data indicates a mechanism by which activated microglia and astrocytes become selectively more sensitive to inflammatory chemokines during CNS disease, and the paper discusses which of the many chemokines present in CNS would have priority of action on microglia and astrocytes. (C) 2003 Elsevier Science B.V. All rights reserved.