Dysferlin is a new marker for leaky brain blood vessels in multiple sclerosis
Dysferlin is a new marker for leaky brain blood vessels in multiple sclerosis
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DOI：
10.1097/01.jnen.0000235119.52311.16
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发表时间：
2006-09-01
影响因子：
3.2
通讯作者：
Lassmann, Hans
中科院分区：
文献类型：
--
作者：
Hochmeister, Sonja;Grundtner, Roland;Lassmann, Hans
Dysferlin是一种参与细胞膜修复的肌肉蛋白，其缺乏与肌营养不良症有关。我们描述了dysferlin也在渗漏的内皮细胞中表达。在正常中枢神经系统（CNS）中，dysferlin仅存在于室周器官的内皮细胞中。在患有多发性硬化症（MS）的患者的发炎CNS中或在患有实验性自身免疫性脑脊髓炎的动物中，在内皮细胞中诱导dysferlin反应性，并且表达与血清蛋白的血管渗漏相关。在MS中，dysferlin在内皮细胞中的表达不限于具有炎症袖的血管，但也存在于非炎症血管中。此外，许多血管周围炎性浸润的血管在非活动性病变或外观正常的白色物质中缺乏dysferlin表达。在体外，dysferlin可以通过用肿瘤坏死因子-α刺激在内皮细胞中诱导。因此，dysferlin不仅是渗漏脑血管的标志物，而且还揭示了多发性硬化症中血管周围炎性浸润和血脑屏障障碍的分离。
Dysferlin is a muscle protein involved in cell membrane repair and its deficiency is associated with muscular dystrophy. We describe that dysferlin is also expressed in leaky endothelial cells. In the normal central nervous system (CNS), dysferlin is only present in endothelial cells of circumventricular organs. In the inflamed CNS of patients with multiple sclerosis (MS) or in animals with experimental autoimmune encephalomyclitis, dysferlin reactivity is induced in endothelial cells and the expression is associated with vascular leakage of serum proteins. In MS, dysferlin expression in endothelial cells is not restricted to vessels with inflammatory cuffs but is also present in noninflamed vessels. In addition, many blood vessels with perivascular inflammatory infiltrates lack dysferlin expression in inactive lesions or in the normal-appearing white matter. In vitro, dysferlin can be induced in endothelial cells by stimulation with tumor necrosis factor-alpha. Hence, dysferlin is not only a marker for leaky brain vessels, but also reveals dissociation of perivascular inflammatory infiltrates and blood-brain barrier disturbance in multiple sclerosis.