Kanmogne Georgette D, Primeaux Charles, Grammas Paula
Department of Pharmacology, Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, Nebraska 68198-5215, USA.
J Neuropathol Exp Neurol. 2005 Jun;64(6):498-505. doi: 10.1093/jnen/64.6.498.
Breakdown of the blood-brain barrier (BBB) is commonly seen in patients with HIV-associated dementia (HAD) despite the lack of productive infection of the brain endothelium. It is likely that secreted viral products play a major role in BBB damage and the development of HAD. The objective of this study is to determine the effects of gp120 proteins on brain endothelial cell permeability and junctional protein expression. Our results showed that treatment of cultured human brain endothelial cells with gp120 for 24 hours results in increased permeability of the endothelial monolayer. Also, gp120 proteins caused disruption and downregulation of the tight junction proteins ZO-1, ZO-2, and occludin in these cells. Other junctional proteins such as claudin-1 and claudin-5 were unaffected by gp120 treatment. These data demonstrate that HIV gp120 proteins alter both the functional and molecular properties of the BBB, which could increase trafficking of HIV, infected cells, and toxic humoral factors into the central nervous system and contribute to the pathogenesis of HAD.
尽管脑内皮细胞未发生有效感染，但血脑屏障（BBB）破坏在人类免疫缺陷病毒相关痴呆（HAD）患者中很常见。分泌的病毒产物可能在血脑屏障损伤和HAD的发展中起主要作用。本研究的目的是确定gp120蛋白对脑内皮细胞通透性和连接蛋白表达的影响。我们的结果表明，用gp120处理培养的人脑内皮细胞24小时会导致内皮单层通透性增加。此外，gp120蛋白导致这些细胞中紧密连接蛋白ZO-1、ZO-2和闭合蛋白的破坏和下调。其他连接蛋白，如claudin-1和claudin-5，不受gp120处理的影响。这些数据表明，HIV gp120蛋白改变了血脑屏障的功能和分子特性，这可能会增加HIV、受感染细胞和毒性体液因子进入中枢神经系统的运输，并导致HAD的发病机制。
