Myeloid microvesicles are a marker and therapeutic target for neuroinflammation
Myeloid microvesicles are a marker and therapeutic target for neuroinflammation
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DOI：
10.1002/ana.23627
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发表时间：
2012-10-01
影响因子：
11.2
通讯作者：
Furlan, Roberto
中科院分区：
文献类型：
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作者：
Verderio, Claudia;Muzio, Luca;Furlan, Roberto
目的：微泡（MV）已被指示为细胞间通讯的重要介质，并正在成为组织损伤的新的生物标志物。我们以前的数据表明，反应性小胶质细胞/巨噬细胞在体外释放MV。该研究的目的是评估MV是否由小胶质细胞/巨噬细胞在体内释放，以及它们的数量是否在脑炎症条件下变化，例如多发性硬化症（MS）。采用电子显微镜、荧光显微镜和流式细胞术检测健康对照、MS患者和实验性自身免疫性脑脊髓炎（EAE）啮齿动物脑脊液（CSF）中的髓样MV，结果：正常对照组CSF中检测到髓样MV。在复发和缓解期EAE小鼠中，CSF中髓样MV的浓度显著增加，并与病程密切相关。对来自2个独立队列的28例复发患者和28例临床孤立综合征患者CSF中的MV进行分析，发现髓样MV水平高于13例年龄匹配的对照，表明MV作为捕获疾病活动的伴随工具具有临床价值。发现髓样MV在体外和体内给药部位传播炎症信号; MV脱落受损的小鼠免受EAE的影响，表明MV在疾病中的致病作用。最后，FTY 720，第一个批准的口服MS药物，显着减少MVs的EAE治疗mice.Interpretation的CSF中的量：这些发现确定髓样MVs作为脑炎症的标记物和治疗靶点。神经网络2012;72：610624
Objective: Microvesicles (MVs) have been indicated as important mediators of intercellular communication and are emerging as new biomarkers of tissue damage. Our previous data indicate that reactive microglia/macrophages release MVs in vitro. The aim of the study was to evaluate whether MVs are released by microglia/macrophages in vivo and whether their number varies in brain inflammatory conditions, such as multiple sclerosis (MS).Methods: Electron and fluorescence microscopy and flow cytometry were used to detect myeloid MVs in the cerebrospinal fluid (CSF) of healthy controls, MS patients, and rodents affected by experimental autoimmune encephalomyelitis (EAE), the animal model of MS.Results: Myeloid MVs were detected in CSF of healthy controls. In relapsing and remitting EAE mice, the concentration of myeloid MVs in the CSF was significantly increased and closely associated with disease course. Analysis of MVs in the CSF of 28 relapsing patients and 28 patients with clinical isolated syndrome from 2 independent cohorts revealed higher levels of myeloid MVs than in 13 age-matched controls, indicating a clinical value of MVs as a companion tool to capture disease activity. Myeloid MVs were found to spread inflammatory signals both in vitro and in vivo at the site of administration; mice impaired in MV shedding were protected from EAE, suggesting a pathogenic role for MVs in the disease. Finally, FTY720, the first approved oral MS drug, significantly reduced the amount of MVs in the CSF of EAE-treated mice.Interpretation: These findings identify myeloid MVs as a marker and therapeutic target of brain inflammation. ANN NEUROL 2012;72:610624