title: Impaired activity of protease inhibitors towards neutrophil elastase bound to human articular cartilage.
abstract: OBJECTIVE
  To investigate the effects of protease inhibitors on the ability of free and cartilage bound neutrophil elastase to degrade cartilage proteoglycan in vitro.
  
  
  METHODS
  Cryostat sections of human articular cartilage were used as substrate, and proteoglycan loss induced by free or cartilage bound elastase was quantified by alcian blue staining, followed by scanning and integrating microdensitometry.
  
  
  RESULTS
  High molecular mass protease inhibitors (alpha 1 protease inhibitor, alpha 2 macroglobulin, and soya bean trypsin inhibitor) and synovial fluid from patients with rheumatoid arthritis were effective in blocking proteoglycan loss from sections treated with free elastase, but their activity towards cartilage bound elastase was much reduced. In contrast, low molecular mass elastase inhibitors (N-methoxysuccinyl-Ala-Ala-Pro-Val chloromethyl ketone and ONO-5046 (N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulphonylamino]benzoyl] amino-acetic acid) were effective against free and cartilage bound elastase.
  
  
  CONCLUSIONS
  The binding of elastase to cartilage appears to be a mechanism whereby the enzyme can remain active in the presence of high molecular mass protease inhibitors.
authors: Department of Experimental Pathology, William Harvey Research Institute, St Bartholomew's Hospital Medical College, London, United Kingdom.
authors: K
authors: K
authors: Kawabata
authors: A R
authors: AR
authors: Moore
authors: D A
authors: DA
authors: Willoughby
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000201:enzymology*; D002358:Cartilage, Articular / Q000201:enzymology*; D046508:Culture Techniques; D006801:Humans; D007700:Kinetics; D019272:Leukocyte Elastase; D008970:Molecular Weight; D010196:Pancreatic Elastase / Q000187:drug effects* / Q000378:metabolism; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011509:Proteoglycans / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism
chemical_list: D011480:Protease Inhibitors; D011509:Proteoglycans; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase