GM-CSF promotes migration of human monocytes across the blood brain barrier
GM-CSF promotes migration of human monocytes across the blood brain barrier
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DOI：
10.1002/eji.201444960
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发表时间：
2015-06-01
影响因子：
5.4
通讯作者：
Dijkstra, Christine D.
中科院分区：
文献类型：
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作者：
Vogel, Daphne Y. S.;Kooij, Gijs;Dijkstra, Christine D.
多发性硬化症（MS）是一种中枢神经系统（CNS）的慢性炎症性脱髓鞘疾病。单核细胞向中枢神经系统的浸润对疾病的发生和发展至关重要。动物研究表明，粒细胞-巨噬细胞集落刺激因子（GM-CSF）可能在这一过程中发挥重要作用，可能通过作用于髓细胞跨越血脑屏障的迁移能力。本研究描述了GM-CSF对人单核细胞、巨噬细胞和小胶质细胞的作用。此外，我们还在健康和病理条件下研究了GM-CSF及其受体在中枢神经系统中的表达。我们表明GM-CSF在体外增强单核细胞跨越人血脑屏障内皮细胞的迁移。接下来，对人脑组织的免疫组织化学分析显示，MS病变中的小胶质细胞和巨噬细胞高度表达GM-CSF。GM-CSF受体在脑灰质/白质合并病变边缘和星形胶质细胞中表达。最后，我们确定了GM-CSF对人巨噬细胞的作用，揭示了一种中间激活状态，其表型类似于在MS活动性病变中观察到的。综上所述，我们的数据表明GM-CSF是单核细胞迁移的强大刺激物，并且在发炎的中枢神经系统中大量存在，在那里它可能作为巨噬细胞和小胶质细胞的激活剂。
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Infiltration of monocytes into the CNS is crucial for disease onset and progression. Animal studies indicate that granulocyte-macrophages colony-stimulating factor (GM-CSF) may play an essential role in this process, possibly by acting on the migratory capacities of myeloid cells across the blood-brain barrier. This study describes the effect of GM-CSF on human monocytes, macrophages, and microglia. Furthermore, the expression of GM-CSF and its receptor was investigated in the CNS under healthy and pathological conditions. We show that GM-CSF enhances monocyte migration across human blood-brain barrier endothelial cells in vitro. Next, immunohistochemical analysis on human brain tissues revealed that GM-CSF is highly expressed by microglia and macrophages in MS lesions. The GM-CSF receptor is expressed by neurons in the rim of combined gray/white matter lesions and astrocytes. Finally, the effect of GM-CSF on human macrophages was determined, revealing an intermediate activation status, with a phenotype similar to that observed in active MS lesions. Together our data indicate that GM-CSF is a powerful stimulator of monocyte migration, and is abundantly present in the inflamed CNS where it may act as an activator of macrophages and microglia.