TNF-alpha opens a paracellular route for HIV-1 invasion across the blood-brain barrier
TNF-alpha opens a paracellular route for HIV-1 invasion across the blood-brain barrier
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DOI：
10.1007/bf03401701
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发表时间：
1997-08-01
影响因子：
5.7
通讯作者：
Kim, KS
中科院分区：
文献类型：
--
作者：
Fiala, M;Looney, DJ;Kim, KS
背景资料：HIV-1在感染后早期侵入中枢神经系统，此时脑内巨噬细胞浸润较低，但髓鞘苍白提示血脑屏障受损。高水平的血浆病毒血症是脑部感染的可能来源。要了解的入侵途径，我们调查了病毒的渗透在体外模型进行对比细胞旁的渗透性TNF-α.材料和方法：血脑屏障模型构建人脑微血管内皮细胞，胎儿星形胶质细胞，和胶原蛋白I或纤连蛋白基质的剂量相关的方式响应细胞因子和配体调节细胞旁的渗透性和细胞迁移。通过感染性和定量HIV-1 RNA测定来测量病毒渗透。使用菊粉或葡聚糖测定屏障渗透性。结果：无细胞的HIV-1被血脑屏障以接近100%的效率保留。TNF-α以与基底通透性成比例的剂量依赖性方式通过细胞旁途径增加病毒渗透。脑内皮细胞是HIV-1的主要屏障。结论：HIV-1感染后早期，血脑屏障对HIV-1感染的脑组织具有保护作用。免疫介质，如TNF-α，打开了病毒进入大脑的细胞旁途径。病毒和病毒蛋白刺激大脑小胶质细胞和巨噬细胞吸引单核细胞进入大脑。浸润的巨噬细胞导致HIV-1脑炎的前进展。
Background: HIV-1 invades the central nervous system early after infection when macrophage infiltration of the brain is low but myelin pallor is suggestive of blood-brain-barrier damage. High-level plasma viremia is a likely source of brain infection. To understand the invasion route, we investigated virus penetration across in vitro models with contrasting paracellular permeability subjected to TNF-alpha.Materials and Methods: Blood-brain-barrier models constructed with human brain microvascular endothelial cells, fetal astrocytes, and collagen I or fibronectin matrix responded in a dose-related fashion to cytokines and ligands modulating paracellular permeability and cell migration. virus penetration was measured by infectious and quantitative HIV-1 RNA assays. Barrier permeability was determined using inulin or dextran. Results: Cell-free HIV-1 was retained by the blood-brain barrier with close to 100% efficiency. TNF-alpha increased virus penetration by a paracellular route in a dose-dependent manner proportionately to basal-permeability. Brain endothelial cells were the main barrier to HIV-1. HIV-1 with monocytes attracted monocyte migration into the brain chamber.Conclusions: Early after the infection, the blood-brain barrier protects the brain from HIV-1. Immune mediators, such as TNF-alpha, open a paracellular route for the virus into the brain. The virus and viral proteins stimulate brain microglia and macrophages to attract monocytes into the brain. infiltrating macrophages cause pro progression of HIV-1 encephalitis.