TNF-related apoptosis-inducing ligand (TRAIL) induces neuronal apoptosis in HIV-encephalopathy

• Published in: Journal of Medical and Dental Sciences Vol. 50; no. 1; pp. 17 - 25
• Main Authors: Miura, Yoshiharu, Koyanagi, Yoshio, Mizusawa, Hidehiro
• Format: Journal Article
• Language: English
• Published: Japan Tokyo Medical and Dental University 01.03.2003
• Subjects: Adult; AIDS Dementia Complex - pathology; Animals; Apoptosis; Apoptosis Regulatory Proteins; Caspase 8; Caspase 9; Caspases - biosynthesis; Cells, Cultured; HIV-1; Humans; In Situ Nick-End Labeling; Macrophages - metabolism; Macrophages - transplantation; Macrophages - virology; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - physiology; Mice; Middle Aged; Neurons - enzymology; Neurons - pathology; TNF-Related Apoptosis-Inducing Ligand; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - physiology
• ISSN: 1342-8810
• DOI: 10.11480/jmds.500103

Neuronal loss is frequently found in brains of patients with human immunodeficiency virus (HIV)-encephalopathy. Extensive apoptosis of neurons is probably involved in the development of HIV-encephalopathy. The present study was designed to investigate the mechanism of neuronal apoptosis. For this purpose, we examined autopsy brains of two patients with HIV-encephalopathy. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells and active forms of caspase-3- and -8-positive cells, including neurons, were found in the perivascular regions of the brains. In these regions, TNF-related apoptosis-inducing ligand (TRAIL)+ macrophages were also observed. We also examined brains of HIV-1-infected mouse model inoculated with human cells. In these brains, TUNEL+ neurons were also found in the perivascular region, the site where infiltrated HIV-1-infected and TRAIL-expressing macrophages were observed. Using an in vitro-culture system, we also demonstrated that the HIV-1-infected monocyte-derived macrophages preferentially expressed TRAIL and that the addition of HIV-1-infected macrophages or human TRAIL-overexpressing mouse cells to cultured mouse primary neurons/glia resulted in neuronal apoptosis. Our results suggest the involvement of TRAIL expressed on HIV-1-infected macrophages in the induction of neuronal apoptosis in infected brain.