TNF-related apoptosis-inducing ligand mediates human neuronal apoptosis: links to HIV-1-associated dementia

• Published in: Journal of neuroimmunology Vol. 148; no. 1; pp. 127 - 139
• Main Authors: Ryan, Lisa A., Peng, Hui, Erichsen, David A., Huang, Yunlong, Persidsky, Yuri, Zhou, You, Gendelman, Howard E., Zheng, Jialin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-03-2004
• Subjects: Acquired Immunodeficiency Syndrome - drug therapy; Adult; AIDS Dementia Complex - drug therapy; AIDS Dementia Complex - pathology; AIDS Dementia Complex - virology; Antibodies, Monoclonal - metabolism; Apoptosis; Apoptosis Regulatory Proteins; Caspase; Caspases - metabolism; Cell Count - methods; Cells, Cultured; Embryo, Mammalian; Enzyme-Linked Immunosorbent Assay - methods; Female; Flow Cytometry - methods; HIV Core Protein p24 - metabolism; HIV-1 encephalitis; Human immunodeficiency virus 1; Humans; Immunohistochemistry - methods; In Situ Nick-End Labeling - methods; Lipopolysaccharides - pharmacology; Macrophage; Male; Membrane Glycoproteins - metabolism; Membrane Glycoproteins - therapeutic use; Microtubule-Associated Proteins - metabolism; Middle Aged; Monocytes - drug effects; Neurons - drug effects; Neurons - pathology; Neurotoxicity; Receptors, TNF-Related Apoptosis-Inducing Ligand; Receptors, Tumor Necrosis Factor - metabolism; TNF-Related Apoptosis-Inducing Ligand; TRAIL; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factor-alpha - pharmacology; Tumor Necrosis Factor-alpha - therapeutic use; Zidovudine - therapeutic use; Caspase; Neurotoxicity; TRAIL; Macrophage; Apoptosis; HIV-1 encephalitis
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2003.11.019

TNF-related apoptosis-inducing ligand (TRAIL) is a type II integral membrane protein that interacts with multiple receptors and cell types including neurons. In this report, TRAIL protein levels were increased in human monocyte-derived macrophages (MDM) after HIV-1 infection and immune activation. In HIV-1 encephalitic (HIVE) human brain tissue, TRAIL-expressing macrophages were found in association with active caspase-3 positive neurons. Cytotoxic TRAIL receptors 1 and 2 were expressed on neurons in primary human fetal cultures and HIV-1 encephalitic brain tissue. Furthermore, TRAIL induced a dose-dependent effect on neuronal apoptosis. These results support a role for TRAIL in mononuclear phagocyte (MP)-mediated neurotoxicity in HIV-1-associated dementia (HAD).