title: Non-proteolytic activation of latent human neutrophil collagenase and its role in matrix destruction in periodontal diseases.
abstract: Collagenases are known to be associated with tissue destruction in chronic inflammatory diseases such as periodontal diseases and rheumatoid arthritis. Collagenases are secreted by circulating inflammatory cells (polymorphonuclear leukocytes and monocytes), resident mesenchymal cells and epithelial cells in latent forms, which can be activated by proteases and compounds reacting with protein thiol groups. We have studied here the effects of oxygen-derived free radicals (ODFR) on latent human neutrophil collagenase. Also, in order to elucidate the cellular sources of collagenases, the ability of human gingival crevicular fluid (GCF) collagenases both from adult periodontitis (AP) and localized juvenile periodontitis (LJP) patients to degrade soluble interstitial collagen types I and II was studied. ODFR generated by the xanthine oxidase/hypoxanthine system in the presence of trace amounts of iron and EDTA activated latent neutrophil collagenase to an equal extent as the known activators phenylmercuric chloride and gold thioglucose. ODFR activation was inhibited by desferoxamine and mannitol as well as by superoxide dismutase and catalase. Clear differences in the susceptibility of collagen types I and II to AP and LJP GCF collagenases were observed. AP GCF collagenase degraded type I and II collagens at equal rates, resembling the substrate-specificity of human neutrophil collagenase. LJP GCF collagenase degraded type I collagen considerably faster than type II collagen, which was only negligibly degraded. This corresponds to the substrate specificity of fibroblast collagenase. Zymographic evaluation of gelatinolytic proteases showed the presence of 90 and 68 kD gelatinases in both AP and LJP GCF. Non-proteolytic means apparently provide a potent activation pathway of neutrophil collagenase in vivo and the hydroxyl radical was identified to be one of the potent activating oxidants.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medical Chemistry, University of Helsinki, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Sorsa
authors.forename: H
authors.initials: H
authors.lastname: Saari
authors.forename: Y T
authors.initials: YT
authors.lastname: Konttinen
authors.forename: K
authors.initials: K
authors.lastname: Suomalainen
authors.forename: S
authors.initials: S
authors.lastname: Lindy
authors.forename: V J
authors.initials: VJ
authors.lastname: Uitto
mesh_terms: D001826:Body Fluids / Q000201:enzymology; D003094:Collagen / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism*; D005609:Free Radicals; D005881:Gingiva / Q000201:enzymology; D006801:Humans; D003012:Microbial Collagenase / Q000097:blood* / Q000302:isolation & purification / Q000502:physiology; D008970:Molecular Weight; D009504:Neutrophils / Q000201:enzymology*; D010100:Oxygen / Q000494:pharmacology*; D010510:Periodontal Diseases / Q000201:enzymology* / Q000378:metabolism
chemical_list: D005609:Free Radicals; D003094:Collagen; D003012:Microbial Collagenase; D010100:Oxygen