Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients
Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients
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DOI：
10.1172/jci5150
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发表时间：
1999-03-01
影响因子：
15.9
通讯作者：
Ransohoff, RM
中科院分区：
文献类型：
--
作者：
Sorensen, TL;Tani, M;Ransohoff, RM
趋化因子通过特定的白细胞群体指导组织侵入。因此，趋化因子可能在多发性硬化症（MS）中发挥作用，多发性硬化症是一种特发性疾病，其中中枢神经系统（CNS）炎症反应主要限于单核吞噬细胞和T细胞。我们通过分析脑脊液（CSF）（其成分反映了CNS细胞外间隙）来询问急性脱髓鞘事件期间CNS中是否表达了特定的趋化因子。在多发性硬化症发作期间，我们发现脑脊液中三种趋化因子水平升高，这些趋化因子作用于T细胞和单核吞噬细胞：干扰素-γ-诱导蛋白。10 kDa（IP-10）;由干扰素-γ诱导的单核因子（Mig）;以及在活化、正常T细胞表达和分泌时受调节（RANTES）。然后，我们研究了特定的趋化因子受体是否表达的浸润细胞在脱髓鞘MS脑病变和脑脊液。CXCR 3是一种IP-10/Mig受体，在活动性MS病变中几乎所有血管周围炎性浸润的淋巴细胞上表达。在活动性脱髓鞘MS脑病变中的淋巴细胞、巨噬细胞和小胶质细胞上检测到CCR 5，一种RANTES受体。与循环T细胞相比，CSF T细胞显著富集表达CXCR 3或CCR 5的细胞。我们的研究结果意味着特定的趋化因子-趋化因子受体相互作用在MS中的致病作用，并为治疗干预提出了新的分子靶点。
Chemokines direct tissue invasion by specific leukocyte populations. Thus, chemokines may play a role in multiple sclerosis (MS), an idiopathic disorder in which the central nervous system (CNS) inflammatory reaction is largely restricted to mononuclear phagocytes and T cells. We asked whether specific chemokines were expressed in the CNS during acute demyelinating events by analyzing cerebrospinal fluid (CSF), whose composition reflects the CNS extracellular space. During MS attacks, we found elevated CSF levels of three chemokines that act toward T cells and mononuclear phagocytes: interferon-gamma-inducible protein. of 10 kDa (IP-10); monokine induced by interferon-gamma (Mig); and regulated on activation, normal T-cell expressed and secreted (RANTES). We then investigated whether specific chemokine receptors were expressed by infiltrating cells in demyelinating MS brain lesions and in CSF. CXCR3, an IP-10/Mig receptor, was expressed on lymphocytic cells in virtually every perivascular inflammatory infiltrate in active MS lesions. CCR5, a RANTES receptor, was detected on lymphocytic cells, macrophages, and microglia in actively demyelinating MS brain lesions. Compared with circulating T cells, CSF T cells were significantly enriched for cells expressing CXCR3 or CCR5. Our results imply pathogenic roles for specific chemokine-chemokine receptor interactions in MS and suggest new molecular targets for therapeutic intervention.