Mice with the beige mutation, which are known to be deficient for leucocyte elastase and cathepsin G, were used to investigate the role of neutral proteases in a model for antigen induced arthritis. Surprisingly, it was shown that in this model of arthritis, using methylated bovine serum albumin as an antigen, C57/black/6 'beige' mice (deficient for leucocyte neutral proteases) developed a more severe form of arthritis than the control mice ('black' mice), resulting in a higher degree of tissue damage. The incidence and degree of bone apposition and destruction of articular cartilage at day 21 after induction of arthritis were significantly higher in the beige mice. These findings could not be ascribed to differences in the cellular immune response to methylated bovine serum albumin. Autoradiographic detection of radiolabelled methylated bovine serum albumin suggested that more antigen is retained in the joints of beige mice than in black mice, which might account for the sustained arthritis and the concomitant tissue damage. These findings do not support the contention that leucocyte elastase and cathepsin G contribute to the pathogenesis of joint destruction in this model.
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