title: Neutrophil-generated free radicals: possible mechanisms of injury in adult respiratory distress syndrome.
abstract: The acute lung injury resulting from adult respiratory distress syndrome (ARDS) is thought to be largely mediated by activated neutrophils. Because activated neutrophils produce the superoxide radical, which is both bacterial and cytotoxic to host cells, this oxygen-derived free radical is likely responsible for at least part of the neutrophil-mediated lung injury. In a rat model of ARDS resulting from intratracheal instillation of interleukin-1, recombinant human manganous superoxide dismutase significantly decreased lung leak. One detrimental action of proteases released by adherent neutrophils may be the degradation of extracellular superoxide dismutase (ECSOD), which normally binds to the heparan sulfate on the surface the endothelium. We found that rabbit ECSOD incubated with either trypsin or activated neutrophils loses affinity for heparin. Furthermore, soluble ECSOD is elevated in the serum of patients with ARDS, consistent with this hypothesis.
authors.affiliation: Webb-Waring Institute for Biomedical Research, University of Colorado Health Sciences Center, Denver 80262.
authors.forename: J M
authors.initials: JM
authors.lastname: McCord
authors.forename: B
authors.initials: B
authors.lastname: Gao
authors.forename: J
authors.initials: J
authors.lastname: Leff
authors.forename: S C
authors.initials: SC
authors.lastname: Flores
mesh_terms: D000818:Animals; D005110:Extracellular Space / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D010539:Permeability; D011817:Rabbits; D051381:Rats; D017382:Reactive Oxygen Species; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000209:etiology*; D013482:Superoxide Dismutase / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology
chemical_list: D007375:Interleukin-1; D017382:Reactive Oxygen Species; D006493:Heparin; D013482:Superoxide Dismutase; D014357:Trypsin