Chemokines and chemokine receptors in inflammatory demyelinating neuropathies: a central role for IP-10
Chemokines and chemokine receptors in inflammatory demyelinating neuropathies: a central role for IP-10
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DOI：
10.1093/brain/awf070
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发表时间：
2002-04-01
期刊：
影响因子：
14.5
通讯作者：
Hartung, HP
中科院分区：
文献类型：
--
作者：
Kieseier, BC;Tani, M;Hartung, HP
炎症细胞募集是PNS自身免疫性脱髓鞘疾病发病机制中的重要一步。在免疫介导的炎症过程中，趋化因子可能在促进白细胞进入神经系统方面发挥关键作用。在此，我们报告了从经典格林-巴利综合征（急性炎症性脱髓鞘性多发性神经根神经病）、慢性炎症性脱髓鞘性多发性神经根神经病和各种非炎症性神经病患者的腓肠神经活检中获得的趋化因子受体 CCR-1、CCR-2、CCR-4、CCR-5 和 CXCR-3 的表达模式。在炎症性脱髓鞘性神经病中通过免疫组织化学检测到一致的趋化因子受体表达模式，并且对标记的单核细胞进行定量显示与对照相比，细胞计数显着升高。 CCR-1和CCR-5主要由神经内膜巨噬细胞表达，而CCR-2、CCR-4和CXCR-3可定位于入侵的T淋巴细胞。定量分析表明，与其他受体相比，浸润 T 细胞中 CXCR-3 的表达量最高。因此，CXCR-3 的表达和分布表明该受体在趋化因子介导的淋巴细胞运输至发炎的三七总皂甙组织中的特定作用。因此，我们进一步分析了其配体干扰素γ诱导蛋白10 kDa（IP-10）和干扰素γ诱导的单核因子（Mig）的表达。在患有炎性神经病的患者的脑脊液中可以测量到 IP-10 水平显着升高，而对于 Mig 则没有观察到差异。 IP-10 mRNA 的原位杂交反映了发炎的 PNS 内同源受体的分布，并将内皮细胞描绘为 IP-10 的主要细胞来源。我们的结果表明特定趋化因子受体和 IP-10 在炎症性脱髓鞘性神经病的发生中具有致病作用。
inflammatory cell recruitment is an important step in the pathogenesis of autoimmune demyelinating diseases of the PNS. Chemokines might play a critical role in promoting leucocyte entry into the nervous system during immune-mediated inflammation. Here, we report the expression pattern of the chemokine receptors CCR-1, CCR-2, CCR-4, CCR-5 and CXCR-3 in sural nerve biopsies obtained from patients with classical Guillain-Barre syndrome (acute inflammatory demyelinating polyradiculoneuropathy), chronic inflammatory demyelinating polyradiculoneuropathy and various non-inflammatory neuropathies. A consistent chemokine receptor expression pattern was immunohistochemically detected in inflammatory demyelinating neuropathies and quantitation of labelled mononuclear cells revealed significantly elevated cell counts compared with controls. CCR-1 and CCR-5 were primarily expressed by endoneurial macrophages, whereas CCR-2, CCR-4 and CXCR-3 could be localized to invading T lymphocytes. Quantitative analysis revealed that CXCR-3 was expressed at highest numbers by infiltrating T cells compared with the other receptors. Thus, expression and distribution of CXCR-3 suggest a specific role of this receptor in chemokine-mediated lymphocyte traffic into the inflamed PNS tissue. Therefore, we further analysed the expression of its ligands interferon-gamma-inducible protein of 10 kDa (IP-10) and monokine induced by interferon-gamma (Mig). Significantly increased levels of IP-10 could be measured in the CSF of patients with inflammatory neuropathies, whereas no differences were observable for Mig. In situ hybridization for IP-10 mRNA mirrored the distribution of the cognate receptor within the inflamed PNS, and delineated endothelial cells as the primary cellular source of IP-10. Our results imply a pathogenic role for specific chemokine receptors and IP-10 in the genesis of inflammatory demyelinating neuropathies.