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

J Neuroimmunol. 2004 Mar;148(1-2):127-39. doi: 10.1016/j.jneuroim.2003.11.019.

Abstract

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).

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS Dementia Complex / drug therapy
  • AIDS Dementia Complex / pathology*
  • AIDS Dementia Complex / virology
  • Acquired Immunodeficiency Syndrome / drug therapy
  • Adult
  • Antibodies, Monoclonal / metabolism
  • Apoptosis Regulatory Proteins
  • Apoptosis*
  • Caspases / metabolism
  • Cell Count / methods
  • Cells, Cultured
  • Embryo, Mammalian
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Flow Cytometry / methods
  • HIV Core Protein p24 / metabolism
  • Humans
  • Immunohistochemistry / methods
  • In Situ Nick-End Labeling / methods
  • Lipopolysaccharides / pharmacology
  • Male
  • Membrane Glycoproteins / metabolism
  • Membrane Glycoproteins / therapeutic use
  • Microtubule-Associated Proteins / metabolism
  • Middle Aged
  • Monocytes / drug effects
  • Neurons / drug effects
  • Neurons / pathology*
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor / metabolism
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Necrosis Factor-alpha / therapeutic use
  • Zidovudine / therapeutic use

Substances

  • Antibodies, Monoclonal
  • Apoptosis Regulatory Proteins
  • HAM-56 antibody
  • HIV Core Protein p24
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Microtubule-Associated Proteins
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFRSF10A protein, human
  • TNFRSF10B protein, human
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • Zidovudine
  • Caspases