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Lookup NU author(s): Dr David Mantle, Gavin Falkous, Dr David Walker
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We have compared (using the same series of experimental samples) the levels of activity of a comprehensive range of cytoplasmic, lysosomal and matrix protease types, together with the levels of free radical-induced protein damage (determined as protein carbonyl derivative) in synovial fluid from rheumatoid (RA) and osteoarthritis (OA) cases. Many protease types showed significantly increased activity (typically by a factor of 2-3-fold) in RA compared to OA cases. Protease activity levels (including those enzyme types putatively involved in the immune response, such as dipeptidyl aminopeptidase IV) in plasma were not significantly different in RA and control cases. The level of free radical induced damage to synovial fluid proteins was approximately 2-fold higher in RA compared to OA, although there was no significant difference in total antioxidant status in synovial fluid or plasma between RA, OA or control cases. We conclude from the above that activation of proteolytic enzymes and free radicals (occurring specifically within synovial tissues) are likely to be of equal potential importance as protein damaging agents in the pathogenesis of RA, and the development of novel therapeutic strategies for the latter disorder should include both protease inhibitory and free radical scavenging elements. In addition, the protease inhibitory element should be designed to inhibit the action of a broad range of enzymic mechanistic types (cysteine, serine, metallo proteinases and peptidases). (C) 1999 Elsevier Science B.V. All rights reserved.
Author(s): Mantle D, Falkous G, Walker D
Publication type: Article
Publication status: Published
Journal: Clinica Chimica Acta
Year: 1999
Volume: 284
Issue: 1
Pages: 45-58
Print publication date: 01/06/1999
ISSN (print): 0009-8981
ISSN (electronic): 1873-3492
Publisher: Elsevier BV
URL: http://dx.doi.org/10.1016/S0009-8981(99)00055-8
DOI: 10.1016/S0009-8981(99)00055-8
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