title: Albumin and hydroxyethyl starch modulate oxidative inflammatory injury to vascular endothelium.
abstract: BACKGROUND
  Human serum albumin is used clinically to maintain colloid osmotic pressure and is viewed to serve an antioxidant role in the vascular compartment via binding of redox-active metal complexes, transport of nitric oxide, and the oxidant-scavenging reactions of the single thiol of human serum albumin, cys34. Because of these potentially desirable adjunctive actions, we evaluated the purity and thiol redox state and compared the relative effects of clinically available 25% human serum albumin preparations with a starch-derived colloid, 6% hydroxyethyl starch, in in vitro models of inflammatory vascular injury.
  
  
  METHODS
  Bovine aortic endothelial cell responses to chemical, enzymatic, and cell-derived reactive inflammatory mediators in the presence of human serum albumin or hydroxyethyl starch were assessed.
  
  
  RESULTS
  The cys34 thiol of fresh human serum albumin preparations was 70-85% oxidized and contained a population of human serum albumin (approximately 25% of total) having the cys34 resistant to reduction by 2-mercaptoethanol and NaBH4. Treatment of bovine aortic endothelial cells with human serum albumin dose-dependently protected from HOCl-mediated 14C-adenine release, with this protective effect of human serum albumin not dependent on protein thiol status. Addition of human serum albumin to cell media provided no protection from the cytotoxic actions of peroxynitrite and xanthine oxidase-derived reactive species. Binding of activated polymorphonuclear leukocytes to bovine aortic endothelial cells was significantly amplified by hydroxyethyl starch and inhibited by human serum albumin administration. The binding of neutrophil-derived myeloperoxidase to bovine aortic endothelial cells, a mediator of multiple oxidative and nitric oxide-consuming reactions, was also inhibited by human serum albumin and enhanced by hydroxyethyl starch.
  
  
  CONCLUSIONS
  Clinical human serum albumin preparations show modest intrinsic non-thiol-dependent antiinflammatory properties in vitro, a phenomenon that was not observed with hydroxyethyl starch.
authors.affiliation: Department of Anesthesiology and Center for Free Radical Biology, The University of Alabama at Birmingham, 35233-6810, USA. John.lang@ccc.uab.edu
authors.forename: John D
authors.initials: JD
authors.lastname: Lang
authors.forename: Mario
authors.initials: M
authors.lastname: Figueroa
authors.forename: Phillip
authors.initials: P
authors.lastname: Chumley
authors.forename: Mutay
authors.initials: M
authors.lastname: Aslan
authors.forename: John
authors.initials: J
authors.lastname: Hurt
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Tarpey
authors.forename: Beatriz
authors.initials: B
authors.lastname: Alvarez
authors.forename: Rafael
authors.initials: R
authors.lastname: Radi
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Freeman
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology*; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000627:therapeutic use*; D009504:Neutrophils / Q000187:drug effects; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000097:blood / Q000378:metabolism; D010952:Plasma Substitutes / Q000627:therapeutic use*; D012709:Serum Albumin / Q000737:chemistry / Q000627:therapeutic use*; D013438:Sulfhydryl Compounds / Q000737:chemistry; D014657:Vasculitis / Q000473:pathology* / Q000517:prevention & control*
chemical_list: D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes; D012709:Serum Albumin; D013438:Sulfhydryl Compounds; D009195:Peroxidase