In vitro induction of neuronal apoptosis by anti-Fas antibody-containing sera from amyotrophic lateral sclerosis patients

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 n...

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Bibliographic Details
Published in:Journal of neuroimmunology 2000-09, Vol.109 (2), p.211-220
Main Authors: Yi, F.H., Lautrette, C., Vermot-Desroches, C., Bordessoule, D., Couratier, P., Wijdenes, J., Preud’homme, J.L., Jauberteau, M.O.
Format: Article
Language:English
Subjects:
Alzheimer disease
Amyotrophic lateral sclerosis
Amyotrophic Lateral Sclerosis - immunology
Animals
Antibodies, Monoclonal - pharmacology
Apoptosis
Apoptosis - drug effects
Apoptosis - immunology
Autoantibodies
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
Fas
Fas antigen
fas Receptor - immunology
Female
Fluorescent Antibody Technique, Indirect
Humans
Immune Sera - pharmacology
In Situ Nick-End Labeling
In Vitro Techniques
Jurkat Cells
Male
Middle Aged
Motoneurons
Motor Neurons - cytology
Motor Neurons - immunology
Neuroblastoma
Rats
Recombinant Proteins - immunology
Tumor Cells, Cultured
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Summary: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.
ISSN:0165-5728
1872-8421
DOI:10.1016/S0165-5728(00)00288-5