Reactive astrocytes express the potassium channel Kir4.1 inactive multiple sclerosis lesions.
Reactive astrocytes express the potassium channel Kir4.1 inactive multiple sclerosis lesions.
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反应性星形胶质细胞表达钾通道 Kir4.1 不活跃的多发性硬化症病变。
DOI：
10.1111/cen3.12011
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Arima K.
中科院分区：
文献类型：
--
作者：
Satoh J;Tabunoki H;Ishida T;Saito Y,Konno H;Arima K.
Kir4.1是一种表达于星形胶质细胞血管周围和突触周围末端足部的内向整流性钾通道，在脑内钾离子的空间缓冲中起着关键作用。最近的一项研究表明，在大约一半的多发性硬化(MS)和临床孤立综合征患者的血清中可以检测到针对Kir4.1的自身抗体，但其发病机制尚需阐明。方法采用免疫组织化学方法研究Kir4.1在多发性硬化(MS)患者和对照脑组织中的表达。结果发现，在MS的活动性脱髓鞘病变、视神经脊髓炎的活动性病变边缘、脑梗塞的缺血灶边缘和阿尔茨海默病的神经退行性病变中，反应性星形胶质细胞表达Kir4.1的强烈免疫反应。活动期MS病变中聚集的反应性星形胶质细胞共表达Kir4.1和AQP4。阿尔茨海默病患者大脑中的一组淀粉样斑块也表达Kir4.1。相比之下，活动期MS病变中浸润的巨噬细胞、活化的小胶质细胞和存活的少突胶质细胞不表达Kir4.1。体外培养的人星形胶质细胞表达Kir4.1，肿瘤坏死因子-α或白介素1β不影响其表达水平，而转化生长因子-β-1可上调其表达水平。结论反应性星形胶质细胞大量表达Kir4.1，且在MS的活动性脱髓鞘病变中不丢失Kir4.1的表达。
ObjectivesKir4.1, an inwardly rectifying potassium channel expressed on perivascular and perisynaptic end‐feet of astrocytes, plays a pivotal role in the spatial buffering of the potassium in the brain. A recent study showed that autoantibodies directed to Kir4.1 are detectable in the serum derived from approximately half of the patients with multiple sclerosis (MS) and clinically isolated syndrome, although their pathogenic roles should be elucidated.MethodsWe studied Kir4.1 expression in MS and control brains by immunohistochemistry.ResultsWe found that reactive astrocytes expressed an intense immunoreactivity for Kir4.1 in active demyelinating lesions of MS, active lesion edges of neuromyelitis optica, ischemic lesion edges of cerebral infarction and neurodegenerative lesions of Alzheimer's disease. Reactive astrocytes accumulated in active MS lesions coexpressed Kir4.1 and AQP4. A subset of amyloid plaques in Alzheimer's disease brains also expressed Kir4.1. In contrast, infiltrating macrophages, activated microglia and surviving oligodendrocytes in active MS lesions did not express Kir4.1. Furthermore, cultured human astrocytes expressed Kir4.1, and the expression levels were not altered by exposure to tumor necrosis factor‐α or interleukin‐1β, but were elevated by transforming growth factor‐β1.ConclusionsThese results show that reactive astrocytes abundantly express Kir4.1, and Kir4.1 immunoreactivity is not lost in active demyelinating lesions of MS.