Oxygen radicals as effectors of cartilage destruction. Direct degradative effect on matrix components and indirect action via activation of latent collagenase from polymorphonuclear leukocytes.
Degradation of intact cartilaginous tissue (bovine nasal cartilage) by oxygen-derived free radicals (ODFR) generated enzymatically by xanthine oxidase and hypoxanthine was studied. The degree of tissue destruction was determined by measuring the indentation under a defined compression force as well as by the loss of uronic acid- and hydroxyproline-containing matrix components. Cartilage slices altered by prior elastase treatment were more susceptible to oxygen radical attack than were intact tissue specimens. Degradation of cartilage matrix by ODFR was strongly inhibited by superoxide dismutase or catalase. Coincubation of latent collagenase from polymorphonuclear leukocytes with the ODFR-generating system led to activation of collagenolytic activity, resulting in marked degradation of the bovine cartilage slices. In further studies, activated polymorphonuclear leukocyte-collagenase was shown to degrade intact human articular cartilage to a degree of mechanical insufficiency. Thus, our assay system serves as an in vitro model of tissue damage, which may be relevant to pathophysiologic states such as rheumatoid arthritis.
D000818:Animals; D002356:Cartilage / Q000187:drug effects*; D002358:Cartilage, Articular / Q000187:drug effects; D002417:Cattle; D004789:Enzyme Activation / Q000187:drug effects; D005110:Extracellular Space / Q000201:enzymology; D006801:Humans; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000494:pharmacology; D003012:Microbial Collagenase / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology*; D013481:Superoxides / Q000494:pharmacology*; D013997:Time Factors; D014969:Xanthine Oxidase / Q000494:pharmacology
D007042:Hypoxanthines; D013481:Superoxides; D019271:Hypoxanthine; D014969:Xanthine Oxidase; D003012:Microbial Collagenase