Chemokines and receptors in HIV encephalitis : AIDS (original) (raw)

ARTICLES

Sanders, Virginia J.1,2; Pittman, Christopher A.1; White, Michael G.1; Wang, Guoji1; Wiley, Clayton A.1; Achim, Cristian L.1

1Department of Pathology, Division of Neuropathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

2Requests for reprints to: Dr Virginia Sanders, PUH A515 Division of Neuropathology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA.

Sponsorship: Supported by NIH grants T32 A1–07487–3 (to V.J.S.), MH46790, and MH55810.

Date of receipt: 22 December 1997; revised: 12 February 1998; accepted: 18 February 1998.

Abstract

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 β-chemokines monocyte chemotactic protein-1, macrophage inflammatory protein-1α, and RANTES were detected on brain macrophages. Their presence was associated with the histopathological signs of HIV encephalitis. The α-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.