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. Copyright © 1990 American College of Rheumatology