The anti-endotoxic effects of the KSL-W decapeptide on Escherichia coli O55:B5 and various oral lipopolysaccharides.
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.
Dixon
D R
DR
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
Karimi-Naser
L
L
Darveau
R P
RP
Leung
K P
KP
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
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