COMPARATIVE IMMUNOLOCALIZATION STUDIES OF COLLAGENASE-1 AND COLLAGENASE-3 PRODUCTION IN THE RHEUMATOID LESION, AND BY HUMAN CHONDROCYTES AND SYNOVIOCYTES IN-VITRO

The degradation of fibrillar type II collagen is a major feature of ca rtilage destruction in rheumatoid arthritis (RA). Since collagenase 3 is produced by chondrocytes and preferentially. degrades type II carti lage collagen, it seemed likely that this enzyme would have a prominen t role in the destruction of rheumatoid joints. Using immunolocalizati on techniques, we have examined and compared the production and distri butions of collagenase 1 and collagenase 3 in cells and tissues derive d from rheumatoid knee arthroplasties. Primary cultures of chondrocyte s stimulated with interleukin-1 beta showed that most of the cells pro duced collagenase 1, whereas only a minority (similar to 5-10%) produc ed collagenase 3; a few chondrocytes demonstrated the co-ordinate prod uction of both enzymes. Primary cultures of rheumatoid synoviocytes pr oduced collagenase 1, but not collagenase 3. Both enzymes were demonst rated in the rheumatoid lesion. Collagenase 1 was more commonly observ ed in both synovium and cartilage (22 of the 28 specimens), was especi ally prominent at cartilage erosion sites, and most of the positive sp ecimens demonstrated extracellular enzyme. By contrast, collagenase 3 was observed less frequently (7/28 specimens) and was produced by rela tively few chondrocytes and synovial cells, this usually being much le ss than that observed for chondrocytes of osteoarthritic cartilage. Th ese observations suggest different regulatory mechanisms for the produ ction of collagenases 1 and 3 in the rheumatoid lesion, and demonstrat e that the distribution and production of collagenase 1 are far more p revalent than those for collagenase 3.