Chemokines and receptors in HIV encephalitis.
BACKGROUND
Chemokines are involved in the migration of leukocytes and have been implicated in several inflammatory diseases of the central nervous system. Some of their receptors have been proposed to mediate HIV infection.


OBJECTIVE
To determine changes in chemokine and receptor expression in HIV encephalitis, and to determine whether upregulation leads to recruitment of infected monocytes across the blood-brain barrier and participates in HIV neuropathology.


METHODS
Immunocytochemistry and double-label immunofluorescent laser confocal microscopy was performed with antibodies to chemokines and their receptors on brain tissues from patients who died with or without HIV encephalitis. In vivo distribution was compared with in vitro cultures of human neuroglial cells.


RESULTS
The beta-chemokines monocyte chemotactic protein-1, macrophage inflammatory protein-1alpha, and RANTES were detected on brain macrophages. Their presence was associated with the histopathological signs of HIV encephalitis. The alpha-chemokines IP-10 (10 kDa inflammatory protein) and interleukin-8 were expressed by astrocytes in all tissues, including controls. Presence of the CXC-chemokine receptor (CXCR)-4 was seen on brain macrophages/microglia, neurons, and astrocytes. CC-Chemokine receptor (CCR)-5 was detected only on macrophages/microglia. CCR-3 and CCR-1 were expressed by macrophages and endothelial cells. In vitro studies examining the presence of CCR-3, CCR-5, and CXCR-4 on human brain cell cultures demonstrated abundant neuronal and microglial expression.


CONCLUSIONS
Expression of a variety of chemokines and receptors was shown to be increased in HIV encephalitis brain tissues particularly in areas of neuroglial reaction. The expression pattern supported their involvement in the recruitment of inflammatory infiltrates and formation of microglial nodules. Presence of chemokine receptors on neurons may be involved in the pathogenesis of neurologic damage in AIDS patients.
Sanders
V J
VJ
Department of Pathology, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA.
Pittman
C A
CA
White
M G
MG
Wang
G
G
Wiley
C A
CA
Achim
C L
CL
D015526:AIDS Dementia Complex / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism; D054357:Chemokine CXCL10; D018925:Chemokines / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism; D018792:Encephalitis, Viral / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D015658:HIV Infections / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D054389:Receptors, CCR1; D054397:Receptors, CCR3; D054398:Receptors, CCR4; D019713:Receptors, CCR5 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism*
C515300:CCR1 protein, human; C515350:CCR3 protein, human; C515354:CCR4 protein, human; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; D019402:Macrophage Inflammatory Proteins; D054389:Receptors, CCR1; D054397:Receptors, CCR3; D054398:Receptors, CCR4; D019713:Receptors, CCR5; D019707:Receptors, Chemokine