Degradation of human articular cartilage by neutrophils in synovial fluid

Abstract

Objective. To determine whether surface‐adherent immunoglobulins are capable of mediating synovial fluid (SF) neutrophil degradation of proteoglycan and collagen in intact, normal human articular cartilage, and to define the respective roles of neutrophil serine proteases and metalloproteases in degrading these cartilage constituents.Methods. Pellet explants of normal human articular cartilage pretreated with bovine serum albumin (BSA) or IgG were incubated with polymorphonuclear cells suspended in SF (PMN‐SF), or with supernatants derived from neutrophils stimulated with surface‐associated IgG. Proteoglycan degradation was measured by assaying release of 35S‐proteoglycan fragments from cartilage explants prelabeled with 35S‐sulfate. Collagen degradation was measured by assaying hydroxyproline content in the PMN‐SF preparations or neutrophil supernatants following their incubation with unlabeled explants.Results. Significant release of both 35S fragments and hydroxyproline was noted following incubation of PMN‐SF with IgG‐treated pellets, compared with pellets treated with BSA. IgG preparations derived from pooled normal serum or rheumatoid arthritis SF were equally efficacious in mediating PMN degradation of cartilage collagens. Explant release of 35S fragments during incubation with PMN supernatant was completely inhibited when serine proteases were inactivated by diisopropyl fluorophosphate (DFP); however, release of 35S fragments was enhanced when metalloprotease activity was present in the supernatant. Release of hydroxyproline during incubation of explants with PMN supernatant was comparable in the presence of DFP or EDTA, but was markedly enhanced when both serine and metalloprotease activity were present in the supernatant.Conclusion. Neutrophils in SF are capable of degrading both proteoglycans and collagens in intact human articular cartilage. Degradation of these cartilage constituents is facilitated by immunoglobulins adherent to the cartilage surface and by the synergistic action of PMN serine and metalloproteases released during activation of neutrophils with surface‐associated immunoglobulin.

Neutralization of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Reduces Spinal Cord Injury Damage in Mice

“…The reduced neutrophil recruitment represents an important additional mechanism for the protective effects of the anti-TRAIL treatment. Neutrophils recruited into the tissue can, in fact, contribute to tissue destruction by the production of reactive oxygen metabolites (Carlson et al, 1998;Tator, 1995), granule enzymes, and cytokines that further amplify the inflammatory response by their effects on macrophages and lymphocytes (Chatham et al, 1993).…”

Neutrophils: Molecules, Functions and Pathophysiological Aspects

“…Neutrophils concentrate at the pannus-cartilage junction, which is the site of early cartilage erosion. They are thought to contribute directly to the cartilage damage, through their serine-and metalloproteases (Chatham et al, 1993;Larbre et al, 1995), as well as through the production of ROS and chlorinated oxidants (Edwards and Hallett, 1997). One should emphasize the importance of neutrophil-and macrophage-derived cytokines, found in large quantities in synovial fluids [eg IL-1␤, IL-6, TNF-␣, TGF-␤, and IL-8].…”

Reprogramming of a subpopulation of human blood neutrophils by prolonged exposure to cytokines

“…Indeed, the activity of infiltrating neutrophils has been intimately linked to disease evolution in a variety of clinical conditions. [2][3][4][5][6][7] Thus, these cells contribute not only to acute inflammatory reactions, but also to the evolution of a variety of chronic inflammatory diseases.…”