Cytotoxic mechanisms in inflammatory myopathies. Co-expression of Fas and protective Bcl-2 in muscle fibres and inflammatory cells
| Autor: | Margaret A. Johnson, A Bender, Reinhard Hohlfeld, Lüder Behrens |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Adult
Male musculoskeletal diseases Pathology medicine.medical_specialty Programmed cell death Adolescent Uracil Nucleotides T-Lymphocytes Muscle Fibers Skeletal Biotin Fluorescent Antibody Technique Apoptosis Inflammation DNA Fragmentation Biology Dermatomyositis Muscular Dystrophies medicine Humans Cytotoxic T cell fas Receptor Aged Staining and Labeling Middle Aged Fas receptor medicine.disease Molecular biology Proto-Oncogene Proteins c-bcl-2 Child Preschool Female Neural cell adhesion molecule Neurology (clinical) medicine.symptom Inclusion body myositis Uracil nucleotide |
| Zdroj: | Brain. 120:929-938 |
| ISSN: | 1460-2156 |
| DOI: | 10.1093/brain/120.6.929 |
| Popis: | Expression of the Fas 'death receptor', Fas (CD95/APO-1) renders cells susceptible to programmed cell death ('apoptosis'), whereas Bcl-2 protects cells from apoptosis. Using fluorescence immunohistochemistry, we analysed Fas and Bcl-2 expression in muscle from five patients with polymyositis (PM), four patients with inclusion body myositis (IBM), three patients with dermatomyositis (DM), three patients with Duchenne muscular dystrophy (DMD) and three nonmyopathic controls. Fas (CD95) and Bcl-2 were not detected in control muscle, but expressed in muscle fibres and inflammatory cells in PM, IBM, DM and DMD. The proportion of Fas+ muscle fibres ranged from < 1 to 50%, and was higher in PM and IBM than in DM and DMD. On average, the Fas+ muscle fibres were smaller (median diameter, 10 microns; range, 7-32 microns) than the Fas- fibres (median, 36 microns; range, 10-60 microns). Less than 10% of the Fas+ muscle fibres co-expressed the regeneration marker CD56 (neural cell adhesion molecule N-CAM). In PM and IBM, the proportion of Fas+ muscle fibres was higher among fibres invaded or contacted by T cells than among fibres not contacted by T cells (P < 0.01). The proportion of Fas+ fibres co-expressing Bcl-2 was 76 +/- 16% in PM, 100% in IBM and 63 +/- 23% in DM. Fas and Bcl-2 expression was also noted in inflammatory cells in PM, IBM, DM and DMD. Using the terminal deoxytransferase-catalysed DNA nick end labelling technique for detection of nuclear DNA fragmentation, none of myonuclei, and < 0.1% of inflammatory cell nuclei, showed signs of apoptosis. Our results suggest that, although Fas expression confers susceptibility to Fas-mediated apoptosis, Fas-expressing muscle fibres and inflammatory cells are protected by the anti-apoptotic protein Bcl-2. |
| Databáze: | OpenAIRE |
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