Imaging correlates of leukocyte accumulation and CXCR4/CXCL12 in multiple sclerosis.
Imaging correlates of leukocyte accumulation and CXCR4/CXCL12 in multiple sclerosis.
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DOI：
10.1001/archneurol.2008.512
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发表时间：
2009-01
影响因子：
--
通讯作者：
Ransohoff, Richard M.
中科院分区：
文献类型：
--
作者：
Moll, Natalia M.;Cossoy, Michael B.;Fisher, Elizabeth;Staugaitis, Susan M.;Tucky, Barbara H.;Rietsch, Anna M.;Chang, Ansi;Fox, Robert J.;Trapp, Bruce D.;Ransohoff, Richard M.
比较慢性多发性硬化（MS）脑MRI定义的感兴趣区域（ROI）中白细胞蓄积和趋化因子受体/配体对CXCR 4/CXCL 12的表达。我们研究了以下ROI：NAWM（正常显示的白色物质）; T2-only（仅T2-WI异常区域）; T2/T1/MTR（T2加权、T1加权图像（-WI）和磁化转移率（MTR）异常区域）。对5例继发性进展性MS（SPMS）病例进行MRI-病理相关性分析。根据影像学特征，切除30个ROI。使用免疫组化，我们评估了髓鞘状态，白细胞积累和CXCR 4/CXCL 12的表达在MS ROI和白色物质区域从5个非神经系统对照病例。10个T2/T1/MTR区域中有8个是慢性活动性或慢性非活动性脱髓鞘病变，而10个仅T2区域中只有2个是脱髓鞘的，并被表征为活动性或慢性活动性病变。与NAWM相比，有髓鞘T2区存在相同数量的CD 68+白细胞（主要细胞类型）。与仅T2区域和NAWM相比，T2/T1/MTR ROI中的实质T细胞显著增加。在仅T2和T2/T1/MTR病变的反应性小胶质细胞和巨噬细胞上发现CXCR 4和磷酸化CXCR 4的表达。CXCL 12免疫反应性检测星形胶质细胞，星形胶质细胞的过程和血管元素在发炎的MS病变。与NAWM相比，T2信号异常的有髓鞘MS ROI中的炎性白细胞积聚并未增加。CXCR 4/CXCL 12在MS病变中的炎性成分上的稳健表达突出了这种趋化因子/受体对在CNS炎症中的作用。
To compare leukocyte accumulation and expression of the chemokine receptor/ligand pair, CXCR4/CXCL12, in MRI-defined regions of interest (ROIs) from chronic multiple sclerosis (MS) brains. We studied the following ROIs: NAWM (normal appearing white matter); T2-only (regions abnormal only on T2-WI); T2/T1/MTR (regions abnormal on T2-weighted, T1-weighted images (-WI) and magnetization transfer ratio (MTR). MRI-pathology correlations were performed on five secondary progressive MS (SPMS) cases. Based on imaging characteristics, thirty ROIs were excised. Using immunohistochemistry, we evaluated myelin status, leukocyte accumulation and CXCR4/CXCL12 expression in the MS ROIs and white matter regions from five non-neurological control cases. Eight of ten T2/T1/MTR regions were chronic-active or chronic-inactive demyelinated lesions, whereas only two of ten T2-only regions were demyelinated and characterized as active or chronic active lesions. Equivalent numbers of CD68+ leukocytes (the predominant cell type) were present in myelinated T2-only regions as compared to NAWM. Parenchymal T-cells were significantly increased in T2/T1/MTR ROIs as compared to T2-only regions and NAWM. Expression of CXCR4 and phospho-CXCR4 was found on reactive microglia and macrophages in T2-only and T2/T1/MTR lesions. CXCL12 immunoreactivity was detected in astrocytes, astrocytic processes and vascular elements in inflamed MS lesions. Inflammatory leukocyte accumulation was not increased in myelinated MS ROIs with abnormal T2 signal as compared with NAWM. Robust expression of CXCR4/CXCL12 on inflammatory elements in MS lesions highlights a role of this chemokine/receptor pair in CNS inflammation.
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影响因子：
9.9
作者：
Moll, N. M.;Rietsch, A. M.;Ransohoff, R. M.
通讯作者：
Ransohoff, R. M.
影响因子：
3.3
作者：
Flynn, G;Maru, S;Male, D
通讯作者：
Male, D
影响因子：
6
作者：
McCandless, Erin E.;Piccio, Laura;Klein, Robyn S.
通讯作者：
Klein, Robyn S.
影响因子：
14.5
作者：
Rovaris, M;Bozzali, M;Filippi, M
通讯作者：
Filippi, M
影响因子：
6
作者：
Brück, W
通讯作者：
Brück, W