CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: A potential mechanism of HIV-CNS invasion and NeuroAIDS
CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: A potential mechanism of HIV-CNS invasion and NeuroAIDS
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DOI：
10.1523/jneurosci.3863-05.2006
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发表时间：
2006-01-25
影响因子：
5.3
通讯作者：
Berman, JW
中科院分区：
文献类型：
--
作者：
Eugenin, EA;Osiecki, K;Berman, JW
与获得性免疫缺陷综合征（AIDS）相关的脑炎和痴呆的特征在于白细胞浸润到CNS中、小胶质细胞活化、异常的趋化因子表达、血脑屏障（BBB）破坏和最终的神经元损失。人类免疫缺陷病毒1型（HIV- 1）感染白细胞是否影响其对趋化因子的迁移反应和改变血脑屏障完整性的能力还知之甚少。我们现在证明，HIV感染的人白细胞的结果，在我们的组织培养模型的人血脑屏障中，在响应于趋化因子CCL 2，以及在破坏血脑屏障，增加渗透性，减少紧密连接蛋白，和基质金属蛋白酶（MMP）-2和MMP-9的表达所证明的增加transmigration。加入到我们的模型中的HIV感染的细胞在没有CCL 2的情况下不迁移，这种情况也不改变BBB的完整性。趋化因子CXCL 10/10 kDa的干扰素-γ-诱导蛋白、CCL 3/巨噬细胞炎性蛋白-1 α或CCL 5/ RANTES（受正常T细胞表达和分泌的活化调节）不增强HIV感染的白细胞迁移或BBB渗透性。HIV感染的白细胞对CCL 2的应答能力的增加与其CCR 2（CCL 2的趋化因子受体）表达的增加相关。这些数据表明，CCL 2，而不是其他趋化因子，在HIV感染的白细胞浸润到CNS和随后的NeuroAIDS的病理学特征中起关键作用。
Encephalitis and dementia associated with acquired immunodeficiency syndrome ( AIDS) are characterized by leukocyte infiltration into the CNS, microglia activation, aberrant chemokine expression, blood-brain barrier (BBB) disruption, and eventual loss of neurons. Little is known about whetherhumanimmunodeficiency virus 1 (HIV- 1) infection of leukocytes affects their ability to transmigrate in response to chemokines and to alter BBB integrity. We now demonstrate that HIV infection of human leukocytes results in their increased transmigration across our tissue culture model of the human BBB in response to the chemokine CCL2, as well as in disruption of the BBB, as evidenced by enhanced permeability, reduction of tight junction proteins, and expression of matrix metalloproteinases (MMP)-2 and MMP-9. HIV-infected cells added to our model did not transmigrate in the absence of CCL2, nor did this condition alter BBB integrity.The chemokines CXCL10/interferon-gamma-inducible protein of 10 kDa, CCL3/ macrophage inflammatory protein-1 alpha, or CCL5/ RANTES ( regulated on activation normal T-cell expressed and secreted) did not enhance HIV-infected leukocyte transmigration or BBB permeability. The increased capacity of HIV- infected leukocytes to transmigrate in response to CCL2 correlated with their increased expression of CCR2, the chemokine receptor for CCL2. These data suggest that CCL2, but not other chemokines, plays a key role in infiltration of HIV- infected leukocytes into the CNS and the subsequent pathology characteristic of NeuroAIDS.