Interaction between neutrophil-derived elastase and reactive oxygen species in cartilage degradation.
The role of proteases and reactive oxygen species (ROS) in polymorphonuclear neutrophil (PMN) induced cartilage degradation in vitro were studied. ONO-5046, a novel synthetic elastase inhibitor, significantly and dose dependently protected cartilage from degradation induced by PMNs stimulated with phorbol myristate acetate (PMA), opsonized zymosan, N-formyl-methionyl-leucyl-phenylalanine plus cytochalasin-B, or A-23187. The degradation by PMA-stimulated PMNs was unaffected by protease inhibitors which lack anti-elastase activity. However, the hydrogen peroxide (H2O2) reducing agent catalase afforded significant protection. Measurement of elastase activity following PMN activation by PMA showed that antioxidants which reduce H2O2 and/or hypochlorous acid decreased elastase activity. Thus, it is suggested that an indirect interaction between ROS and elastase activity may exist in PMN induced cartilage degradation. Furthermore, the possible implication of an endogenous elastase inhibitor(s) is discussed.
Iwamura
H
H
Department of Experimental Pathology, William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, UK.
Moore
A R
AR
Willoughby
D A
DA
D000818:Animals; D002356:Cartilage / Q000378:metabolism*; D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004789:Enzyme Activation; D005966:Glucuronidase / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D019272:Leukocyte Elastase; D008163:Luminescent Measurements; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012697:Serine Endopeptidases; D013449:Sulfonamides / Q000494:pharmacology
D017382:Reactive Oxygen Species; D013449:Sulfonamides; C069195:sivelestat; D005966:Glucuronidase; D002403:Cathepsins; D012697:Serine Endopeptidases; D056649:Cathepsin G; C534097:Ctsg protein, rat; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D005998:Glycine