title: The cellular distribution of extracellular superoxide dismutase in macrophages is altered by cellular activation but unaffected by the naturally occurring R213G substitution.
abstract: Extracellular superoxide dismutase (EC-SOD) is responsible for the dismutation of the superoxide radical produced in the extracellular space and known to be expressed by inflammatory cells, including macrophages and neutrophils. Here we show that EC-SOD is produced by resting macrophages and associated with the cell surface via the extracellular matrix (ECM)-binding region. Upon cellular activation induced by lipopolysaccharide, EC-SOD is relocated and detected both in the cell culture medium and in lipid raft structures. Although the secreted material presented a significantly reduced ligand-binding capacity, this could not be correlated to proteolytic removal of the ECM-binding region, because the integrity of the material recovered from the medium was comparable to that of the cell surface-associated protein. The naturally occurring R213G amino acid substitution located in the ECM-binding region of EC-SOD is known to affect the binding characteristics of the protein. However, the analysis of macrophages expressing R213G EC-SOD did not present evidence of an altered cellular distribution. Our results suggest that EC-SOD plays a dynamic role in the inflammatory response mounted by activated macrophages.
authors: Department of Biomedicine, Aarhus University, DK-8000 Aarhus, Denmark.
authors: Randi H
authors: RH
authors: Gottfredsen
authors: Department of Medicine, National Jewish Health, Denver, CO 80206, USA.
authors: David A
authors: DA
authors: Goldstrohm
authors: Department of Medicine, National Jewish Health, Denver, CO 80206, USA.
authors: John M
authors: JM
authors: Hartney
authors: Department of Biomedicine, Aarhus University, DK-8000 Aarhus, Denmark.
authors: Ulrike G
authors: UG
authors: Larsen
authors: Department of Medicine, National Jewish Health, Denver, CO 80206, USA.
authors: Russell P
authors: RP
authors: Bowler
authors: Department of Biomedicine, Aarhus University, DK-8000 Aarhus, Denmark. Electronic address: svp@biokemi.au.dk.
authors: Steen V
authors: SV
authors: Petersen
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D005109:Extracellular Matrix / Q000187:drug effects; D005110:Extracellular Space / Q000201:enzymology; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000201:enzymology* / Q000648:ultrastructure; D051379:Mice; D009154:Mutation; D009504:Neutrophils / Q000201:enzymology* / Q000648:ultrastructure; D011485:Protein Binding / Q000187:drug effects; D013482:Superoxide Dismutase / Q000737:chemistry / Q000235:genetics* / Q000648:ultrastructure; D013481:Superoxides / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D013481:Superoxides; C499090:Sod3 protein, mouse; D013482:Superoxide Dismutase
keywords: Antioxidant; Extracellular superoxide dismutase; Free radicals; Inflammation; Macrophage