Degradation of cartilage proteoglycan by human leukocyte granule neutral proteases--a model of joint injury. I. Penetration of enzyme into rabbit articular cartilage and release of 35SO4-labeled material from the tissue.
J Clin Invest, 1976/3;57(3):615-24.
Janoff A, Feinstein G, Malemud CJ, Elias JM
PMID: 129482
Impact factor: 19.456
Abstract
The present work was undertaken to explore the effect of two purified neutral proteases derived from human peripheral blood polymorphonuclear leukocytes (PMN) on articular cartilage as a model of joint injury. Human leukocyte elastase and chymotrypsin-like enzyme, purified by affinity chromatography, released 32SO4 from labeled rabbit articular cartilage slices in vitro. Release of isotope was initially delayed, suggesting that either a lag in enzyme penetration occurs or that size of degradation fragments is a limiting factor in diffusion of label out of the tissue. The release of 35SO4 was inhibited by preincubation of elastase and chymotrypsin-like enzyme with human alpha 1-anti-trypsin, or with their specific chloromethyl ketone inactivators, and the action of elastase was also inhibited by a monospecific antiserum to PMN elastase, freed of major serum proteinase inhibitors. Immunohistochemical staining procedures revealed the presence of PMN elastase inside the matrix of cartilage slices after a 20-min exposure of tissue to either the pure enzyme or crude PMN granule extract. Serum alpha 1-antitrypsin failed to penetrate into the cartilage slices under identical in vitro conditions. In association with the results reported in the accompanying paper, these findings suggest a model of cartilage matrix degradation by PMN neutral proteases in which local protease-antiprotease imbalance, coupled with different rates of penetration of protease and antiprotease into target tissue, plays a key role in accounting for matrix damage.
MeSH terms
Animals; Cartilage, Articular; Chymotrypsin; Cytoplasmic Granules; Disease Models, Animal; Enzyme Inhibitors; Glycosaminoglycans; Humans; Immune Sera; Joint Diseases; Kinetics; Leukocytes; Oligopeptides; Pancreatic Elastase; Peptide Hydrolases; Phenylalanine; Proteoglycans; Rabbits; Sulfur Radioisotopes; alpha 1-Antitrypsin
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