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Rheumatology 2001; 40: 55-61
© 2001 British Society for Rheumatology

Human granzyme B mediates cartilage proteoglycan degradation and is expressed at the invasive front of the synovium in rheumatoid arthritis

H. K. Ronday1,2, W. H. van der Laan1,3, P. P. Tak4, J. A. D. M. de Roos1, R. A. Bank1, J. M. TeKoppele1, C. J. Froelich5, C. E. Hack6, P. C. W. Hogendoorn5, F. C. Breedveld3 and J. H. Verheijen1,

1 Gaubius Laboratory, TNO Prevention and Health, Leiden,
2 Department of Rheumatology, Leyenburg Hospital, The Hague,
3 Department of Rheumatology University Hospital, Leiden,
4 Division of Clinical Immunology and Rheumatology, Academic Medical Center, Amsterdam,
5 Department of Pathology, University Hospital, Leiden,
6 Laboratory of The Netherlands Red Cross Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Amsterdam, The Netherlands

Objective. To investigate the cartilage-degrading capacity of granzyme B and the presence of granzyme B-positive cells at sites of erosion in the rheumatoid synovium.

Methods. Granzyme B was added to [3H]proline/[35S]sulphate-labelled cartilage matrices and to cartilage explants. Proteoglycan degradation was assessed by the release of 35S and glycosaminoglycans into the medium and collagen degradation was assessed by the release of 3H and hydroxyproline and by measuring the fraction of denatured collagen. Granzyme B expression was studied at the invasive front of the synovium by immunohistochemistry.

Results. Granzyme B induced loss of both newly synthesized, radiolabelled proteoglycans in cartilage matrices and resident proteoglycans of the cartilage explants. No effect on collagen degradation was found. Granzyme B-positive cells were present throughout the synovium and at the invasive front.

Conclusion. The presence of granzyme B-positive cells at the invasive front of the synovium together with its ability to degrade articular proteoglycans supports the view that granzyme B may contribute to joint destruction in rheumatoid arthritis.

KEY WORDS: Granzyme B, Cartilage destruction, Rheumatoid arthritis.

Correspondence to: J. H. Verheijen, Gaubius Laboratory, TNO Prevention and Health, PO Box 2215, 2301 CE Leiden, The Netherlands.


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