THE POSSIBLE ROLE OF NEUTROPHIL PROTEINASES IN DAMAGE TO ARTICULAR-CARTILAGE

The proteolytic degradation of articular cartilage that is seen in the arthritides affects both of the major structural components of the tissue, proteoglycan and collagen. Neutrophil leucocytes are abundant in the synovial fluid of the inflamed joints, and we have considered whether the large quantities of neutral proteinases carried by these cells could contribute to the cartilage degradation. The two neutrophil serine proteinases have been isolated, and shown to break down both proteoglycan and collagen in articular cartilage. The enzymes attacked the non-helical terminal peptides of the collagen, eliminating the cross-links, thus destabilizing and solubilizing the fibres. The soluble collagen then denatured spontaneously, and was further degraded. Although large quantities of the neutrophil proteinases are probably released in the synovial fluid each day, the inhibitory capacity of the fluid is seldom, if ever, saturated. Nevertheless, immunologically mediated release of the neutrophil enzymes in 'frustrated endocytosis' at the cartilage surface could give rise to the generalized damage that has been reported by others.