TY - JOUR
T1 - Immunohistochemical analysis of CCR2, CCR3, CCR5, and CXCR4 in the human brain
T2 - Potential mechanisms for HIV dementia
AU - Van der Meer, Peter
AU - Ulrich, Anthony M.
AU - Gonalez-Scarano, Francisco
AU - Lavi, Ehud
N1 - Funding Information:
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.
PY - 2000
Y1 - 2000
N2 - 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. (C) 2000 Academic Press.
AB - 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. (C) 2000 Academic Press.
KW - CCR2
KW - CCR3
KW - CCR5
KW - CXCR4
KW - Central nervous system (CNS)
KW - Chemokine receptor
KW - HIV-1
KW - HIV-related dementia
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U2 - 10.1006/exmp.2000.2336
DO - 10.1006/exmp.2000.2336
M3 - Article
C2 - 11115360
AN - SCOPUS:0034537408
VL - 69
SP - 192
EP - 201
JO - Experimental and Molecular Pathology
JF - Experimental and Molecular Pathology
SN - 0014-4800
IS - 3
ER -