Temporal expression and cellular origin of CC chemokine receptors CCR1, CCR2 and CCR5 in the central nervous system: insight into mechanisms of MOG-induced EAE.
Temporal expression and cellular origin of CC chemokine receptors CCR1, CCR2 and CCR5 in the central nervous system: insight into mechanisms of MOG-induced EAE.
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DOI：
10.1186/1742-2094-4-14
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发表时间：
2007-05-07
影响因子：
9.3
通讯作者：
Sunnemark D
中科院分区：
文献类型：
--
作者：
Eltayeb S;Berg AL;Lassmann H;Wallström E;Nilsson M;Olsson T;Ericsson-Dahlstrand A;Sunnemark D
CC趋化因子受体CCR1、CCR2和CCR5在多发性硬化症（MS）和其他神经炎性疾病中对单核吞噬细胞向中枢神经系统（CNS）募集至关重要。单核吞噬细胞是能够吞噬髓磷脂和破坏轴突的效应细胞。在本研究中，我们对髓鞘少突胶质细胞糖蛋白诱导的实验性自身免疫性脑脊髓炎（MOG-EAE）大鼠脊髓中CCR1、CCR2和CCR5 mRNA的区域、时间和细胞表达进行了表征。虽然与人类多发性硬化症相似，但该动物模型允许从复发的神经炎症的不同时间点和不同病变阶段（早期活动性、晚期活动性和非活动性完全脱髓鞘病变）获取中枢神经系统组织。采用射频标记的cRNA探针，结合免疫组织化学染色对表型细胞标志物进行原位杂交，研究CCR1、CCR2和CCR5 mRNA的表达。对健康大鼠和MOG-EAE大鼠（急性期、缓解期、复发期）的脊髓切片进行分析。在确定的病变阶段，测定表达CCR1、CCR2和CCR5 mRNA的细胞数量。数据采用非参数Mann-Whitney U检验进行统计学分析。在MOG-EAE大鼠中，在活动性炎症和脱髓鞘发作期间，脊髓中发现CCR1和CCR5 mRNA广泛上调，CCR2 mRNA适度上调。表型细胞标记双染色鉴定趋化因子受体mrna表达细胞为巨噬细胞/小胶质细胞。在临床缓解期间，所有三种受体的表达均显著降低，与脊髓炎症和脱髓鞘减少相一致。健康对照大鼠在脊髓中未显示任何可检测到的CCR1、CCR2或CCR5 mRNA表达。我们的研究结果表明，MOG-EAE的急性和慢性复发期与CCR1、CCR2和CCR5 mRNA在中枢神经系统病变内的巨噬细胞/小胶质细胞谱系的不同表达有关。这些数据支持CCR1、CCR2和CCR5介导浸润性巨噬细胞和常驻小胶质细胞募集到中枢神经系统炎症部位的观点。详细了解表达模式对于理解治疗调节和验证CCR1、CCR2和CCR5作为MS治疗干预的可行靶点至关重要。
The CC chemokine receptors CCR1, CCR2 and CCR5 are critical for the recruitment of mononuclear phagocytes to the central nervous system (CNS) in multiple sclerosis (MS) and other neuroinflammatory diseases. Mononuclear phagocytes are effector cells capable of phagocytosing myelin and damaging axons. In this study, we characterize the regional, temporal and cellular expression of CCR1, CCR2 and CCR5 mRNA in the spinal cord of rats with myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE). While resembling human MS, this animal model allows unique access to CNS-tissue from various time-points of relapsing neuroinflammation and from various lesional stages: early active, late active, and inactive completely demyelinated lesions. The expression of CCR1, CCR2 and CCR5 mRNA was studied with in situ hybridization using radio labelled cRNA probes in combination with immunohistochemical staining for phenotypic cell markers. Spinal cord sections from healthy rats and rats with MOG-EAE (acute phase, remission phase, relapse phase) were analysed. In defined lesion stages, the number of cells expressing CCR1, CCR2 and CCR5 mRNA was determined. Data were statistically analysed by the nonparametric Mann-Whitney U test. In MOG-EAE rats, extensive up-regulation of CCR1 and CCR5 mRNA, and moderate up-regulation of CCR2 mRNA, was found in the spinal cord during episodes of active inflammation and demyelination. Double staining with phenotypic cell markers identified the chemokine receptor mRNA-expressing cells as macrophages/microglia. Expression of all three receptors was substantially reduced during clinical remission, coinciding with diminished inflammation and demyelination in the spinal cord. Healthy control rats did not show any detectable expression of CCR1, CCR2 or CCR5 mRNA in the spinal cord. Our results demonstrate that the acute and chronic-relapsing phases of MOG-EAE are associated with distinct expression of CCR1, CCR2, and CCR5 mRNA by cells of the macrophage/microglia lineage within the CNS lesions. These data support the notion that CCR1, CCR2 and CCR5 mediate recruitment of both infiltrating macrophages and resident microglia to sites of CNS inflammation. Detailed knowledge of expression patterns is crucial for the understanding of therapeutic modulation and the validation of CCR1, CCR2 and CCR5 as feasible targets for therapeutic intervention in MS.
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影响因子：
4.4
作者：
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