Induction of neutrophil enzyme release by rheumatoid factors: evidence for differences based on molecular characteristics.
Cathepsin G and elastase are two neutrophil proteases capable of degrading the major structural macromolecules of the joint. Evaluation of factors capable of inducing the release of these enzymes is crucial to the understanding of neutrophil-mediated tissue destruction. We have evaluated the effects of IgM rheumatoid factor (RF), as well as monomeric and polymeric forms of IgA RF, on the release of neutrophil elastase, cathepsin G, and the specific granule protein lactoferrin. None of these rheumatoid factors alone was able to induce more lysosomal protein release than media controls. Under conditions used in this study, aggregated human IgG was able to induce slightly more release than media controls. The addition of IgM RF or polymeric IgA RF to the aggregated IgG resulted in release of significantly more lysosomal proteins than aggregates alone. In contrast, monomeric IgA RF, even in the presence of aggregated IgG, was unable to augment enzyme release. These results suggest that differences in the molecular characteristics of RF found in synovial fluid may significantly influence the contribution of RF to tissue injury in rheumatoid arthritis.
D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000276:immunology*; D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D007781:Lactoferrin / Q000378:metabolism*; D007782:Lactoglobulins / Q000378:metabolism*; D008247:Lysosomes / Q000201:enzymology; D009504:Neutrophils / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000378:metabolism*; D012217:Rheumatoid Factor / Q000276:immunology*; D012697:Serine Endopeptidases; D013582:Synovial Fluid / Q000276:immunology
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007782:Lactoglobulins; C034639:polymeric IgA; D012217:Rheumatoid Factor; D002403:Cathepsins; D007781:Lactoferrin; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase