Effect of endothelial cell polarity on β-amyloid-induced migration of monocytes across normal and AD endothelium
Effect of endothelial cell polarity on β-amyloid-induced migration of monocytes across normal and AD endothelium
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DOI：
10.1152/ajpcell.00293.2001
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发表时间：
2002-09-01
影响因子：
5.5
通讯作者：
Kalra, VK
中科院分区：
文献类型：
--
作者：
Giri, R;Selvaraj, S;Kalra, VK
在正常衰老和淀粉样β-肽(Abeta)疾病，如阿尔茨海默病(AD)期间，人们发现Abeta和激活的单核细胞/小胶质细胞在大脑中沉积增加。我们以前的研究表明，Abeta与正常人脑微血管内皮细胞的单层相互作用导致单核细胞的黏附和迁移增加。在AD脑中积累的Abeta在调节外周血单核细胞(PBM)通过血脑屏障(BBB)以及伴随的单核细胞/小胶质细胞在AD脑中的聚集中所起的作用相对较少。在这项研究中，我们发现Abeta(1-40)与来自正常或AD患者的脑内皮细胞(BEC)单层顶面相互作用，导致单核细胞(HL-60和THP-1)和PBM的跨内皮迁移增加。然而，单核细胞在Transwell小室培养的BEC单层上的迁移，当Abeta加入到AD的基底外侧时，比正常的单个BEC增加了2.5倍。在正常和AD-BEC中，抗Abeta受体和抗内皮细胞连接分子-1(PECAM-1)抗体均可抑制Abeta诱导的单核细胞迁移。我们的结论是，Abeta与AD-BEC的基底外侧表面相互作用，诱导细胞信号，促进单核细胞从顶端向基底外侧的迁移。我们认为，AD脑实质或脑血管中的Abeta启动细胞信号，诱导PBM跨血脑屏障迁移并在大脑中积聚。
During normal aging and amyloid beta-peptide (Abeta) disorders such as Alzheimer's disease (AD), one finds increased deposition of Abeta and activated monocytes/microglial cells in the brain. Our previous studies show that Abeta interaction with a monolayer of normal human brain microvascular endothelial cells results in increased adherence and transmigration of monocytes. Relatively little is known of the role of Abeta accumulated in the AD brain in mediating trafficking of peripheral blood monocytes (PBM) across the blood-brain barrier (BBB) and concomitant accumulation of monocytes/microglia in the AD brain. In this study, we showed that interaction of Abeta(1-40) with apical surface of monolayer of brain endothelial cells (BEC), derived either from normal or AD individuals, resulted in increased transendothelial migration of monocytic cells (HL-60 and THP-1) and PBM. However, transmigration of monocytes across the BEC monolayer cultivated in a Transwell chamber was increased 2.5-fold when Abeta was added to the basolateral side of AD compared with normal individual BEC. The Abeta-induced transmigration of monocytes was inhibited in both normal and AD-BEC by antibodies to the putative Abeta receptor, receptor for advanced glycation end products (RAGE), and to the endothelial cell junction molecule, platelet-endothelial cell adhesion molecule-1 (PECAM-1). We conclude that interaction of Abeta with the basolateral surface of AD-BEC induces cellular signaling, promoting transmigration of monocytes from the apical to basolateral direction. We suggest that Abeta in the AD brain parenchyma or cerebrovasculature initiates cellular signaling that induces PBM to transmigrate across the BBB and accumulate in the brain.