title: Reactive oxygen species as regulators of human neutrophil and fibroblast interstitial collagenases.
abstract: The effects of various reactive oxygen species on latent human neutrophil and fibroblast-type interstitial collagenases were studied. Latent human neutrophil collagenases (proMMP-8) was efficiently activated by hypochlorous acid and hydrogen peroxide and less efficiently by the serine proteinases trypsin and chymotrypsin. Human plasmin and plasma kallikrein did not activate latent human neutrophil collagenase. The activation of latent human neutrophil collagenase by hypochlorous acid and hydrogen peroxide corresponded to the activation obtained with the other known non-proteolytic activators phenylmercuric chloride and gold thioglucose. The activation by hydrogen peroxide was inhibited by mannitol and desferoxamine, suggesting a localized Fenton-type reaction to be responsible for the generation of hydroxyl radical and/or hydroxyl radical-like reactive oxygen pathway of neutrophil procollagenase does not involve plasmin and plasma kallikrein, which are efficient proteolytic activators of latent fibroblast-type procollagenase (proMMP-1). Fibroblast procollagenase was also slightly activated by hypochlorous acid and gold thioglucose. Thus neutrophil procollagenase seems to prefer non-proteolytic means of activation and reactive oxygen species can be regarded as potent activators in vivo. Synovial-fluid neutrophils from rheumatoid arthritis patients were found to release collagenase in 30% active form when compared to same patients' peripheral blood neutrophils, which released collagenase in completely latent form. This may indicate that the triggering of neutrophil at the site of inflammation in vivo involves initial oxidative activation of collagenase upon the degranulation process.
authors.affiliation: IVth Department of Medicine, Helsinki University Central Hospital, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Saari
authors.forename: T
authors.initials: T
authors.lastname: Sorsa
authors.forename: O
authors.initials: O
authors.lastname: Lindy
authors.forename: K
authors.initials: K
authors.lastname: Suomalainen
authors.forename: S
authors.initials: S
authors.lastname: Halinen
authors.forename: Y T
authors.initials: YT
authors.lastname: Konttinen
mesh_terms: D017364:Collagenases / Q000378:metabolism*; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D020781:Matrix Metalloproteinase 1; D020784:Matrix Metalloproteinase 8; D009504:Neutrophils / Q000201:enzymology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013582:Synovial Fluid / Q000166:cytology
chemical_list: D017382:Reactive Oxygen Species; D017364:Collagenases; D020784:Matrix Metalloproteinase 8; D020781:Matrix Metalloproteinase 1