CX3CL1 (fractalkine) and CX3CR1 expression in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis: kinetics and cellular origin.
CX3CL1 (fractalkine) and CX3CR1 expression in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis: kinetics and cellular origin.
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CX3CL1（Fractalkine）和CX3CR1在髓磷脂少突胶质细胞糖蛋白诱导的实验自身免疫性脑脊髓炎中：动力学和细胞来源。
DOI：
10.1186/1742-2094-2-17
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发表时间：
2005-07-29
影响因子：
9.3
通讯作者：
Ericsson-Dahlstrand A
中科院分区：
文献类型：
--
作者：
Sunnemark D;Eltayeb S;Nilsson M;Wallström E;Lassmann H;Olsson T;Berg AL;Ericsson-Dahlstrand A
多发性硬化（MS）是中枢神经系统（CNS）的慢性炎症性疾病。它与小胶质细胞和星形胶质细胞的局部活化、活化的巨噬细胞和T细胞的浸润、髓磷脂的主动降解以及轴突和神经元的损伤有关。CX 3CL 1的建议角色（fractalkine）在控制小胶质细胞活化和白细胞浸润中的作用将这种趋化因子及其受体CX 3CR 1置于潜在的战略位置，以控制与MS脑病变发展相关的病理事件的关键方面。在这项研究中，我们通过分析MS中趋化因子及其受体CX 3CR 1的分布、动力学在患有实验诱导的MS样疾病、髓鞘少突胶质细胞糖蛋白（MOG）诱导的自身免疫性脑脊髓炎（EAE）的大鼠的CNS中，CX 3CL 1和CX 3CR 1 mRNA表达的调节和细胞起源。采用放射性标记的cRNA探针原位杂交组织化学方法检测CX 3CL 1及其受体CX 3CR 1的mRNA表达，结合表型细胞标志物的免疫组化染色，研究CX 3CL 1及其受体CX 3CR 1的表达。分析健康大鼠脑和来自患有MOG EAE的大鼠的脑。在确定的MOG EAE病变阶段，通过图像分析确定CX 3CR 1 mRNA表达细胞的数量和原位杂交信号的强度。数据通过ANOVA进行统计学评价，然后进行Tukey\primes多重比较检验。CX 3CL 1 mRNA的表达存在于神经元样细胞位于整个健康大鼠的神经轴。CX 3CL 1的表达在MOG诱导的EAE大鼠的CNS中保持不变，除了在炎性病变内的星形胶质细胞中诱导表达。值得注意的是，健康和脑炎动物的脑血管系统没有表现出CX 3CL 1 mRNA表达的迹象。受体CX 3CR 1由健康大脑所有区域的小胶质细胞表达。MOG诱导的EAE的诱导与炎症性脑损伤内CX 3CR 1 mRNA表达细胞的明显积累相关，其中绝大多数对小胶质细胞-巨噬细胞谱系的标志物染色呈阳性。对时间分期的脑病变的分析显示，斑块周围区的小胶质细胞中CX 3CR 1 mRNA水平升高，以及早期活动、晚期活动和非活动脱髓鞘病变中CX 3CR 1表达细胞的累积显著增强。我们的数据表明，在正常和炎症大鼠大脑中，趋化因子CX 3CL 1及其受体CX 3CR 1分别由神经元/星形胶质细胞和小胶质细胞组成和调节表达。我们的研究结果提出了一种机制，神经元和反应性星形胶质细胞可以控制周围小胶质细胞的迁移和功能。此外，在炎性脑损伤中，表达CX 3CR 1的细胞而不是小胶质细胞的积累表明CX 3CL 1在控制外周白细胞侵入脑中可能起作用。
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). It is associated with local activation of microglia and astroglia, infiltration of activated macrophages and T cells, active degradation of myelin and damage to axons and neurons. The proposed role for CX3CL1 (fractalkine) in the control of microglia activation and leukocyte infiltration places this chemokine and its receptor CX3CR1 in a potentially strategic position to control key aspects in the pathological events that are associated with development of brain lesions in MS. In this study, we examine this hypothesis by analyzing the distribution, kinetics, regulation and cellular origin of CX3CL1 and CX3CR1 mRNA expression in the CNS of rats with an experimentally induced MS-like disease, myelin oligodendrocyte glycoprotein (MOG)-induced autoimmune encephalomyelitis (EAE). The expression of CX3CL1 and its receptor CX3CR1 was studied with in situ hybridization histochemical detection of their mRNA with radio labeled cRNA probes in combination with immunohistochemical staining of phenotypic cell markers. Both healthy rat brains and brains from rats with MOG EAE were analyzed. In defined lesional stages of MOG EAE, the number of CX3CR1 mRNA-expressing cells and the intensity of the in situ hybridization signal were determined by image analysis. Data were statistically evaluated by ANOVA, followed by Tukey\primes multiple comparison test. Expression of CX3CL1 mRNA was present within neuronal-like cells located throughout the neuraxis of the healthy rat. Expression of CX3CL1 remained unaltered in the CNS of rats with MOG-induced EAE, with the exception of an induced expression in astrocytes within inflammatory lesions. Notably, the brain vasculature of healthy and encephalitic animals did not exhibit signs of CX3CL1 mRNA expression. The receptor, CX3CR1, was expressed by microglial cells in all regions of the healthy brain. Induction of MOG-induced EAE was associated with a distinct accumulation of CX3CR1 mRNA expressing cells within the inflammatory brain lesions, the great majority of which stained positive for markers of the microglia-macrophage lineage. Analysis in time-staged brain lesions revealed elevated levels of CX3CR1 mRNA in microglia in the periplaque zone, as well as a dramatically enhanced accumulation of CX3CR1 expressing cells within the early-active, late-active and inactive, demyelinated lesions. Our data demonstrate constitutive and regulated expression of the chemokine CX3CL1 and its receptor CX3CR1 by neurons/astrocytes and microglia, respectively, within the normal and inflamed rat brain. Our findings propose a mechanism by which neurons and reactive astrocytes may control migration and function of the surrounding microglia. In addition, the accumulation of CX3CR1 expressing cells other than microglia within the inflammatory brain lesions indicate a possible role for CX3CL1 in controlling invasion of peripheral leucocytes to the brain.
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影响因子：
4.4
作者：
Boehme, SA;Lio, FM;Conlon, PJ
通讯作者：
Conlon, PJ
影响因子：
15.9
作者：
Haskell, CA;Hancock, WW;Charo, IF
通讯作者：
Charo, IF
影响因子：
2.2
作者：
Imaizumi, T;Matsumiya, T;Satoh, K
通讯作者：
Satoh, K
DOI：
10.1073/pnas.95.18.10896
发表时间：
1998-09-01
影响因子：
11.1
作者：
Harrison, JK;Jiang, Y;Feng, LL
通讯作者：
Feng, LL
影响因子：
3.3
作者：
Chen, SZ;Luo, DF;Harrison, JK
通讯作者：
Harrison, JK