Lysis of fibrillar collagen by neutrophils in synovial fluid. A role for surface-bound immunoglobulins.
Synovial fluids (SF) contain inhibitors capable of neutralizing the activity of proteases secreted by inflammatory cells and fibroblasts. To further define a potential role for SF polymorphonuclear neutrophils (PMN) in mediating joint destruction, peripheral blood PMN were suspended in SF and incubated with reconstituted collagen fibrils. Incubation of PMN-SF mixtures with collagen fibrils precoated with monomeric IgG resulted in significant lysis of the underlying fibrils relative to that seen with uncoated fibrils. Augmented fibril lysis by PMN-SF mixtures in which the PMN were activated with fluid-phase ligands such as phorbol myristate acetate or heat-aggregated IgG was not seen. Lysis of IgG-coated fibrils by PMN-SF was inhibited in the presence of EDTA or sodium azide. PMN-mediated resorption of fibrillar collagen occurred despite the presence of protease inhibitors in the SF at a concentration capable of neutralizing human neutrophil collagenase. These results suggest that the focal release and activation of human neutrophil collagenase during PMN stimulation by tissue-bound immunoglobulins may mediate the resorption of joint tissue collagens in rheumatoid arthritis, even in the presence of protease inhibitors.
Chatham
W W
WW
Division of Clinical Immunology and Rheumatology, Birmingham Veterans Administration Hospital, AL 35233.
Heck
L W
LW
Blackburn
W D
WD
D000818:Animals; D001386:Azides / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology / Q000502:physiology; D008024:Ligands; D003012:Microbial Collagenase / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology*; D051381:Rats; D019810:Sodium Azide; D013582:Synovial Fluid / Q000166:cytology*
D001386:Azides; D007074:Immunoglobulin G; D008024:Ligands; D003094:Collagen; D019810:Sodium Azide; D004492:Edetic Acid; D003012:Microbial Collagenase