In Vitro Induction of Neuronal Apoptosis by anti-Fas Antibody-Containing Sera From Amyotrophic Lateral Sclerosis Patients

J Neuroimmunol. 2000 Sep 22;109(2):211-20. doi: 10.1016/s0165-5728(00)00288-5.

Abstract

Sera from 26% of patients with sporadic amyotrophic lateral sclerosis (ALS) induced in vitro apoptosis of a human neuroblastoma cell line, as detected by two methods, and most contained anti-Fas autoantibodies. In contrast, Alzheimer sera (studied as controls) very rarely induced apoptosis and did not contain detectable anti-Fas antibodies. Soluble Fas-ligand levels in ALS sera were not different from those in normal sera, except for slightly higher levels in a single case. In mixed cultures of rat embryonic brain and spinal cord cells, ALS sera (and agonistic anti-Fas monoclonal antibodies and soluble Fas-ligand) induced the apoptosis of a subpopulation of neurons. These neurons were motoneurons on the basis of staining with the monoclonal antibody SMI 32 and Fas expression was restricted to these SMI 32-positive neurons. These data are compatible with the hypothesis of the participation of an autoimmune mechanism possibly related to anti-Fas autoantibodies in certain ALS patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / immunology*
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / immunology*
  • Autoantibodies / analysis
  • Autoantibodies / pharmacology
  • Blotting, Western
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspase Inhibitors
  • Central Nervous System / cytology
  • Enzyme Inhibitors / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Immune Sera / pharmacology
  • In Situ Nick-End Labeling
  • In Vitro Techniques
  • Jurkat Cells
  • Male
  • Middle Aged
  • Motor Neurons / cytology*
  • Motor Neurons / immunology*
  • Neuroblastoma
  • Rats
  • Recombinant Proteins / immunology
  • Tumor Cells, Cultured
  • fas Receptor / immunology*

Substances

  • Antibodies, Monoclonal
  • Autoantibodies
  • Caspase Inhibitors
  • Enzyme Inhibitors
  • Immune Sera
  • Recombinant Proteins
  • fas Receptor
  • CASP3 protein, human
  • CASP8 protein, human
  • CASP9 protein, human
  • Casp3 protein, rat
  • Casp8 protein, rat
  • Casp9 protein, rat
  • Caspase 3
  • Caspase 8
  • Caspase 9