CYTOTOXIC MECHANISMS IN INFLAMMATORY MYOPATHIES - COEXPRESSION OF FASAND PROTECTIVE BCL-2 IN MUSCLE-FIBERS AND INFLAMMATORY CELLS

Expression of the Fas 'death receptor', Fas (CD95/APO-1) renders cells susceptible to programmed cell death ('apoptosis'), whereas Bcl-2 pro tects cells from apoptosis. Using fluorescence immunohistochemistry, w e analysed Fas and Bcl-2 expression in muscle from five patients with polymyositis (PM), four patients with inclusion body myositis (IBM), t hree patients with dermatomyositis (DM), three patients with Duchenne muscular dystrophy (DMD) and three nonmyopathic controls. Fas (CD95) a nd Bcl-2 were not detected in control muscle, but expressed in muscle fibres and inflammatory cells in PM, IBM, DM and DMD. The proportion o f Fas+ muscle fibres ranged from <1 to 50%, and was higher in PM and I BM than in DM and DMD. On average, the Fas+ muscle fibres were smaller (median diameter 10 mu m; range, 7-32 mu m) than the Fas- fibres (med ian, 36 mu m; range, 10-60 mu m). Less than 10% of the Fas+ muscle fib res co-expressed the regeneration marker CD56 (neural cell adhesion mo lecule 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 P M, IBM, DM and DMD. Using the terminal deoxytransferase-catalysed DNA nick end labelling technique for detection of nuclear DNA fragmentatio n, none of myonuclei, and < 0.1% of inflammatory cell nuclei, showed s igns of apoptosis. Our results suggest that, although Fas expression c onfers susceptibility to Fas-mediated apoptosis, Fas-expressing muscle fibres and inflammatory cells are protected by the anti-apoptotic pro tein Bcl-2.