Activation of latent rheumatoid synovial collagenase by human mast cell tryptase.
The functional role of mast cells in rheumatoid synovium was investigated by assessing the ability of mast cell tryptase to activate latent collagenase derived from rheumatoid synoviocytes. Tryptase, a mast cell neutral protease, was demonstrated in situ to reside in rheumatoid synovial mast cells, by an immunoperoxidase technique using a mouse mAb against tryptase, and in vitro to be released by dispersed synovial mast cells after both immunologic and nonimmunologic challenge. Each rheumatoid synovial mast cell contains an average of 6.2 pg of immunoreactive tryptase and the percent release values of this protease correlated with those of histamine (r = 0.58, p less than 0.01). The ability of purified tryptase to promote collagenolysis was demonstrated in a dose-dependent fashion using latent collagenase derived from rheumatoid synovium, synovial fluid, IL-1-stimulated cultured synoviocytes, and partially purified latent collagenase derived from conditioned media, with between 10 and 92% of the collagen substrate degraded. [3H] Collagen, treated with tryptase-activated latent collagenase, was subjected to electrophoresis on SDS polyacrylamide gels and autoradiography showed the collagen degradation pattern (A, B) characteristically produced by collagenase. Mast cell lysates also activated synovial latent collagenase yielding 24% digestion of collagen substrate. This activator in mast cell lysates could be inhibited by diisopropylflurophosphate or by immunoadsorption of tryptase. Thus, mast cells may activate metalloproteinases and play a role in the catabolism of collagen that occurs in rheumatoid synovium.
D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D002458:Cell Fractionation; D002469:Cell Separation; D004789:Enzyme Activation; D006636:Histamine Release; D006801:Humans; D008407:Mast Cells / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D003012:Microbial Collagenase / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000302:isolation & purification / Q000502:physiology*; D013583:Synovial Membrane / Q000201:enzymology* / Q000276:immunology / Q000473:pathology
D010447:Peptide Hydrolases; C023073:tosylarginine methyl ester hydrolase; D003012:Microbial Collagenase