Regular Article
Immunohistochemical Analysis of CCR2, CCR3, CCR5, and CXCR4 in the Human Brain: Potential Mechanisms for HIV Dementia

https://doi.org/10.1006/exmp.2000.2336Get rights and content
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Abstract

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.

Keywords

CXCR4
CCR2
CCR3
CCR5
central nervous system (CNS)
chemokine receptor
HIV-1
HIV-related dementia.

Cited by (0)

The authors thank Dr. James Hoxie (Department of Medicine, University of Pennsylvania) for the gift of anti-CXCR4 monoclonal antibodies. This work was supported in part by PHS Grants NS-27405 and MH58958.

1

Current address: Medical School, University of Groningen, The Netherlands.

2

To whom reprint requests should be addressed at Division of Neuropathology, University of Pennsylvania School of Medicine, 613 Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104-6100. Fax: (215) 898-9969. E-mail: [email protected].