title: Human mononuclear cells and neutral proteinases. III. Neutral proteinases and rheumatoid arthritis: monocytes as a source of cathepsin G and proteinase potentiation of IgM rheumatoid factor elaboration.
abstract: We have been interested in contributions of certain cells and mediators to synovial inflammation rheumatoid arthritis (RA). The present studies were designed to determine (1) whether monocytes contained the neutral proteinase cathepsin G and (2) if neutral proteinase could induce or potentiate cellular IgM rheumatoid factor (RF) production. Monocyte-rich and monocyte-poor populations were isolated by Ficoll-Hypaque density sedimentation followed by glass adherence, and cellular lysates were obtained by repetitive freezing and thawing as we have reported for neutrophil-derived neutral proteinase. Cathepsin G was quantified immunochemically by an enzyme-linked immunoassay (ELISA) we developed utilizing commercially available anti-cathepsin G antibodies. Mononuclear and B-cell-enriched cell cultures were prepared by standard methods and IgM RF measured by our ELISA. Cell-derived lysates from monocyte-enriched populations (84 +/- 3% monocytes, less than 1% neutrophils) contained considerably greater amounts of measurable cathepsin G (OD280 = 0.393 +/- 0.153) than lysates from equal numbers of monocyte (15 +/- 2% monocytes, less than 1% neutrophils)-depleted cells (OD280 = 0.071 +/- 0.038; P less than 0.05). Eighteen patients with RA and three normal individuals did not have consistently increased cellular elaboration of Ig or IgM RF in vitro in response to proteinase (trypsin) stimulation; however, patients manifested 80% potentiation by trypsin of pokeweed-stimulated cellular IgM RF production in vitro (pokeweed-stimulated IgM RF 137 +/- 53 ng/ml, pokeweed/trypsin-induced IgM RF 246 +/- 100 ng/ml; P less than 0.02), changes being most striking for those patients seropositive by latex fixation test (84% increase, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, College of Medicine, University of Florida, Gainesville.
authors.forename: R S
authors.initials: RS
authors.lastname: Panush
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology*; D001172:Arthritis, Rheumatoid / Q000201:enzymology*; D056649:Cathepsin G; D002403:Cathepsins / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology*; D011043:Pokeweed Mitogens / Q000494:pharmacology; D012217:Rheumatoid Factor / Q000096:biosynthesis*; D012697:Serine Endopeptidases; D014357:Trypsin / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D007075:Immunoglobulin M; D011043:Pokeweed Mitogens; D012217:Rheumatoid Factor; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D014357:Trypsin