van der Meer P, Ulrich A M, Gonźalez-Scarano F, Lavi E
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6100, USA.
Exp Mol Pathol. 2000 Dec;69(3):192-201. doi: 10.1006/exmp.2000.2336.
The CXC chemokine receptor CXCR4 was the first molecule identified as a coreceptor working in conjunction with CD4 to mediate cellular entry for the human immunodeficiency virus (HIV-1). Since that original discovery, 11 other seven-mtransmembrane domain molecules, many of which are chemokine receptors, have been shown to facilitate HIV entry into cells. These include CCR5, CCR3, CCR2, CCR1, CCR8, CX3CR1, STRL33 (BONZO), GPR15 (BOB), GPR1, US28, and APJ. In studies done by this and other labs, CCR3, CCR5, and CXCR4 have been identified in CNS microglia and several laboratories, including ours, have shown that CXCR4 is expressed in neurons. Neuronal expression of CCR2, CCR3, and CCR5 has been less consistent. We performed a semiquantitative immunohistochemical analysis of the expression of CCR2, CCR3, CCR5, and CXCR4 in 23 regions of the brain and in two sections of the spinal cord. Hippocampal neurons were positive for CCR2, CCR3, and CXCR4, but not for CCR5. In other regions of the brain, neurons, and glial cells reacted with anti-CCR2, anti-CCR3, and anti-CXCR4 antibodies, whereas only glial cells (primarily microglia) were positive for CCR5. The areas of highest expression, however, seem to be subcortical regions and the limbic system. The limbic system plays a key role in memory, and the presence of CXCR4-which can bind the viral envelope protein gp120-min a subset of neurons from this system may play a role in the development of HIV-related dementia.
CXC趋化因子受体CXCR4是首个被鉴定为与CD4协同作用介导人类免疫缺陷病毒（HIV-1）细胞进入的共受体分子。自最初发现以来，已证实另外11种七跨膜结构域分子（其中许多是趋化因子受体）可促进HIV进入细胞。这些分子包括CCR5、CCR3、CCR2、CCR1、CCR8、CX3CR1、STRL33（BONZO）、GPR15（BOB）、GPR1、US28和APJ。在本实验室及其他实验室所做的研究中，已在中枢神经系统小胶质细胞中鉴定出CCR3、CCR5和CXCR4，包括我们实验室在内的几个实验室均已表明CXCR4在神经元中表达。CCR2、CCR3和CCR5在神经元中的表达情况不太一致。我们对大脑23个区域和脊髓的两个切片中CCR2、CCR3、CCR5和CXCR4的表达进行了半定量免疫组织化学分析。海马神经元CCR2、CCR3和CXCR4呈阳性，但CCR5呈阴性。在大脑的其他区域，神经元和神经胶质细胞与抗CCR2、抗CCR3和抗CXCR4抗体发生反应，而只有神经胶质细胞（主要是小胶质细胞）CCR5呈阳性。然而，表达最高的区域似乎是皮质下区域和边缘系统。边缘系统在记忆中起关键作用，该系统一部分神经元中存在可结合病毒包膜蛋白gp120的CXCR4，这可能在HIV相关痴呆的发生发展中起作用。
