Increased expression of distinct galectins in multiple sclerosis lesions
Increased expression of distinct galectins in multiple sclerosis lesions
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DOI：
10.1111/j.1365-2990.2011.01184.x
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发表时间：
2011-10-01
影响因子：
5
通讯作者：
Baron, W.
中科院分区：
文献类型：
--
作者：
Stancic, M.;van Horssen, J.;Baron, W.
目的：多发性硬化（MS）是一种慢性进行性中枢神经系统退行性疾病，其特征在于炎症、脱髓鞘、最终髓鞘再生失败和轴突丢失。目前的研究确定半乳糖凝集素，粘附/生长调节效应结合β-半乳糖苷，肽基序和脂质，作为重要的免疫调节剂在各种炎症性疾病。然而，很少有人知道他们的表达，细胞定位和在人类中枢神经系统组织中的作用。为了鉴定半乳糖凝集素在MS中的潜在作用，检查了它们在对照白色物质（CWM）和脱髓鞘MS病变中的表达和定位。方法：采用qPCR、Westernblot和免疫组化方法，对人死后不同时期的CWM和MS病变进行分析。类似地分析了来自健康受试者和MS患者的培养星形胶质细胞。结果如下：在测试的11种不同的半乳糖凝集素中，半乳糖凝集素-1、-3、-8和-9以可检测的水平存在于CWM中，并且有趣的是，在活动性MS病变中显著增强。在细胞水平上，半乳糖凝集素定位于小胶质细胞/巨噬细胞、星形胶质细胞和内皮细胞。有趣的是，当比较活动性和非活动性MS病变时，半乳糖凝集素-9在小胶质细胞/巨噬细胞中显示出明显不同的细胞内定位，在活动性病变中仅限于细胞核，而在非活动性病变中主要定位在细胞质中。此外，从MS患者培养的星形胶质细胞释放增强水平的半乳糖凝集素-1，在Western印迹分析中检测为二聚体。结论：这项研究提供了一个详细的分析半乳糖凝集素在MS病变，并分配不同的半乳糖凝集素的疾病的不同方面。因此，除了被称为炎症过程的调节剂之外，我们的研究结果还表明不同的半乳糖凝集素与MS病理学存在额外的联系。
Aims: Multiple sclerosis (MS) is a chronic progressive degenerative disorder of the central nervous system, characterized by inflammation, demyelination, ultimate failure of remyelination and axonal loss. Current research identifies galectins, adhesion/growth-regulatory effectors binding beta-galactosides, peptide motifs and lipids, as important immunomodulators in diverse inflammatory diseases. However, little is known about their expression, cellular localization and role in human central nervous system tissue. To identify a potential role of galectins in MS, their expression and localization in control white matter (CWM) and demyelinated MS lesions were examined. Methods: qPCR, Western blot and immunohistochemical analyses were performed on human post mortem CWM and MS lesions at different stages. Cultured astrocytes, derived from healthy subjects and MS patients, were analysed similarly. Results: Among 11 different galectins tested, galectins-1, -3, -8 and -9 were present at detectable levels in CWM, and, interestingly, significantly enhanced in active MS lesions. On the cellular level, galectins localized to microglia/macrophages, astrocytes and endothelial cells. Intriguingly, galectin-9 displayed a distinctly different intracellular localization in microglia/macrophages when comparing active and inactive MS lesions, being restricted to the nuclei in active lesions, and primarily localizing in the cytoplasm in inactive lesions. Furthermore, enhanced levels of galectin-1, detected as dimers in Western blot analysis, were released by cultured astrocytes from MS patients. Conclusions: This study provides a detailed analysis of galectins in MS lesions and assigns distinct galectins to different aspects of the disease. Thus, besides being known as modulators of inflammatory processes, our findings suggest additional association of distinct galectins with MS pathology.