cathepsin-g and Arthritis

Topics: Animals; Arthritis; Cartilage, Articular; Cathepsin G; Cathepsins; History, 20th Century; Humans; Leukocyte Elastase; Neutrophils; Pancreatic Elastase; Serine Endopeptidases

Mice with the beige mutation are known to be deficient for polymorphonuclear leucocyte (PMN) elastase and cathepsin G and can therefore be used as a model for protease dependence of tissue destruction in inflammatory conditions. The in vitro and in vivo effect of PMN activation on cartilage damage in C57black/6 normal and beige mice was measured. In vitro it was found that stimulation of normal PMNs with chemotactic peptide caused degradation of articular cartilage matrix owing to an elastase dependent mechanism; PMNs of beige mice did not induce degradation of cartilage. In vivo, using zymosan induced arthritis, which is a model characterised by a PMN-rich infiltrate and exudate, no significant differences were found between the two strains with respect to (a) joint oedema formation as measured by technetium-99m uptake; (b) matrix degradation as measured quantitatively and with histology; (c) chondrocyte proteoglycan synthesis as measured by radiosulphate uptake. At day 28 after induction of arthritis, when inflammation is waning, no differences in end stage irreversible damage to joint tissues were found. The relevance of these observations to the supposed role of PMN derived neutral proteases in joint inflammation is discussed.

Topics: Animals; Arthritis; Cartilage, Articular; Cathepsin G; Cathepsins; In Vitro Techniques; Male; Mice; Mice, Inbred Strains; Neutrophils; Pancreatic Elastase; Serine Endopeptidases

The collagenolytic activity associated with insoluble collagen fibers separated from homogenates of inflamed paws from rats with adjuvant arthritis was quantitated using EDTA-sensitive solubilization of hydroxyproline as a measure of activity. Approximately 60% of the solubilized hydroxyproline was associated with dialyzable products. The level of collagenolytic activity in the paws increased with time after the induction of adjuvant arthritis and paralleled to a large extent the development of inflammation in both the adjuvant injected (right) hind paw and in the non-injected, contralateral paw. By day 26, the level of free collagenolytic activity in the injected paw had increased to a level 30 times normal while that in the contralateral paw had increased to a level 10 times normal. Treatment of the residues from the injected paws with trypsin resulted in the activation of a latent collagenolytic activity which, on day 26, accounted for approximately 50% of the total activity. The elevated level of collagen prolyl hydroxylase in the inflamed paw suggested that the rate of collagen synthesis was also increased. The activity of beta-glucuronidase increased in the inflamed paw with time after the induction of adjuvant arthritis while that of cathepsin G was elevated as compared to normal in paws removed, 5 but not 22 days after the induction of adjuvant arthritis. The inflamed paw of the adjuvant rat may represent a useful system in which to study the role of collagenolytic enzymes in the destruction of connective tissue by inflammatory lesions.

Topics: Animals; Arthritis; Arthritis, Experimental; Cathepsin G; Cathepsins; Collagen; Disease Models, Animal; Glucuronidase; Male; Microbial Collagenase; Peptide Hydrolases; Procollagen-Proline Dioxygenase; Rats; Serine Endopeptidases; Time Factors