title: The anti-endotoxic effects of the KSL-W decapeptide on Escherichia coli O55:B5 and various oral lipopolysaccharides.
abstract: OBJECTIVE
  Host responses following the recognition of bacterial lipopolysaccharide can range from acute inflammation to septic shock. The aim of this study was to evaluate the ability of the KSL-W decapeptide to bind to and block the endotoxic effects of lipopolysaccharide.
  
  
  METHODS
  An enzyme-linked immunosorbent assay-based binding assay using fluorescently labeled KSL-W to detect adsorbed Escherichia coli O55:B5 lipopolysaccharide was employed. A commercially available recombinant Factor C lipopolysaccharide detection assay, hemagglutination of rabbit erythrocytes as well as E-selectin expression in human umbilical vein endothelial cells were used to assess the anti-endotoxic effects after KSL-W exposure to E. coli lipopolysaccharide as well as to oral lipopolysaccharide samples.
  
  
  RESULTS
  Lipopolysaccharide-binding assays using E. coli O55:B5 lipopolysaccharide revealed both a higher maximal binding range (532-713 microM) and a half-maximum binding concentration (70-185 microM) for the KSL-W peptide when compared with its analog control. Significant inhibition of E-selectin expression in human umbilical vein endothelial cells (p < 0.0001) as well as hemagglutination of rabbit erythrocytes occurred after the interaction of KSL-W with E. coli lipopolysaccharide. Recombinant Factor C enzyme detection inhibition revealed dose-dependent inhibition values ranging from 1.0-51.8 microM. which were dependent upon the type of lipopolysaccharide sample tested.
  
  
  CONCLUSIONS
  These results demonstrate that for the concentrations tested, the KSL-W decapeptide was nontoxic to mammalian cells and could bind to and block the host recognition and response towards enteric, as well as oral, lipopolysaccharide samples.
authors.affiliation: Microbiology and Immunology Branch, US Army Dental and Trauma Research Detachment, Walter Reed Army Institute of Research, Great Lakes Naval Training Station, Great Lakes, IL, USA. douglas.dixon@na.amedd.army.mil
authors.forename: D R
authors.initials: DR
authors.lastname: Dixon
authors.forename: L
authors.initials: L
authors.lastname: Karimi-Naser
authors.forename: R P
authors.initials: RP
authors.lastname: Darveau
authors.forename: K P
authors.initials: KP
authors.lastname: Leung
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans; D000818:Animals; D060829:Arthropod Proteins; D001779:Blood Coagulation Factors / Q000037:antagonists & inhibitors; D047630:Depsipeptides / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D004731:Endotoxins / Q000037:antagonists & inhibitors; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors; D004912:Erythrocytes / Q000187:drug effects; D004926:Escherichia coli; D005456:Fluorescent Dyes; D016967:Fusobacterium nucleatum; D006384:Hemagglutination / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D016966:Porphyromonas gingivalis; D018713:Prevotella intermedia; D011817:Rabbits; D012697:Serine Endopeptidases
chemical_list: D060829:Arthropod Proteins; D001779:Blood Coagulation Factors; D047630:Depsipeptides; D019040:E-Selectin; D004731:Endotoxins; D004792:Enzyme Precursors; D005456:Fluorescent Dyes; D008070:Lipopolysaccharides; C482199:lipopolysaccharide, E coli O55-B5; C119235:lysyl-lysyl-valyl-valyl-phenylalanyl-lysyl-valyl-lysyl-phenylalanyl-lysine; D012697:Serine Endopeptidases; C057151:Limulus clotting factor C