Borrelia burgdorferi, host-derived proteases, and the blood-brain barrier
Borrelia burgdorferi, host-derived proteases, and the blood-brain barrier
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DOI：
10.1128/iai.73.2.1014-1022.2005
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发表时间：
2005-02-01
影响因子：
3.1
通讯作者：
Kim, KS
中科院分区：
文献类型：
--
作者：
Grab, DJ;Perides, G;Kim, KS
莱姆病在人类中的神经学表现部分归因于伯氏疏螺旋体（Borrelia burgdorferi）穿透血脑屏障（BBB）和侵入中枢神经系统（CNS）。然而，螺旋体如何穿过血脑屏障仍然是一个悬而未决的问题。我们研究了B的遍历。使用由人脑微血管内皮细胞（BMEC）和EA.hy926（一种在CostarTranswell插入物上生长的人脐静脉内皮细胞（HUVEC）系）构建的体外模型系统，这些研究表明，B. Burgdorferi差异性地杂交人BMEC和HUVEC，并且人BMEC形成穿越的屏障。在螺旋体的迁移过程中，发现内皮细胞单层的完整性得以维持，如在实验期结束时通过跨内皮电阻测量所评估的，并且B. burgdorferi似乎通过它们的尖端在细胞边界附近或在细胞边界处结合人BMEC，这表明了一种细胞旁的迁移途径。重要的是，遍历B。在人BMEC中的伯氏螺旋体诱导纤溶酶原激活物、纤溶酶原激活物受体和基质金属蛋白酶的表达。因此，通过激活级联连接的纤溶系统可能导致允许B的紧密连接蛋白的局灶性和瞬时降解。burgdorferi入侵中枢神经系统
Neurological manifestations of Lyme disease in humans are attributed in part to penetration of the blood-brain barrier (BBB) and invasion of the central nervous system (CNS) by Borrelia burgdorferi. However, how the spirochetes cross the BBB remains an unresolved issue. We examined the traversal of B. burgdorferi across the human BBB and systemic endothelial cell barriers using in vitro model systems constructed of human brain microvascular endothelial cells (BMEC) and EA.hy 926, a human umbilical vein endothelial cell (HUVEC) line grown on Costar Transwell inserts. These studies showed that B. burgdorferi differentially crosses human BMEC and HUVEC and that the human BMEC form a barrier to traversal. During the transmigration by the spirochetes, it was found that the integrity of the endothelial cell monolayers was maintained, as assessed by transendothelial electrical resistance measurements at the end of the experimental period, and that B. burgdorferi appeared to bind human BMEC by their tips near or at cell borders, suggesting a paracellular route of transmigration. Importantly, traversal of B. burgdorferi across human BMEC induces the expression of plasminogen activators, plasminogen activator receptors, and matrix metalloproteinases. Thus, the fibrinolytic system linked by an activation cascade may lead to focal and transient degradation of tight junction proteins that allows B. burgdorferi to invade the CNS.