title: Lipopolysaccharide from Rhodobacter sphaeroides is an agonist in equine cells.
abstract: Endotoxemia is associated with the principal causes of death in adult horses and equine neonates and, therefore, veterinary researchers are expending efforts to identify new therapeutic interventions that might be beneficial in these animals. Endotoxin antagonists inhibit interaction of endotoxin with cellular receptors and may be beneficial in the treatment of endotoxemia and sepsis. Diphosphoryl lipid A from Rhodobacter sphaeroides (RsDPLA) is a potent antagonist of enteric LPS in human cells, but is an agonist in hamster cells. In this study, the effect of lipopolysaccharide from R. sphaeroides (RsLPS) on equine whole blood and isolated monocyte preparations was investigated by comparing tumor necrosis factor (TNF) production in response to RsLPS and Escherichia coli O55:B5 LPS. Our results indicate that RsLPS is a potent agonist in equine cells, which precludes therapeutic use of this agent in equine patients. In contrast to the results in equine cells, RsLPS did not elicit TNF production by itself, and inhibited the response to E. coli O55:B5 LPS in a human monocytic cell line.
authors.affiliation: Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602, USA.
authors.forename: Katharina L
authors.initials: KL
authors.lastname: Lohmann
authors.forename: Michel
authors.initials: M
authors.lastname: Vandenplas
authors.forename: Michelle H
authors.initials: MH
authors.lastname: Barton
authors.forename: James N
authors.initials: JN
authors.lastname: Moore
mesh_terms: D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D004926:Escherichia coli / Q000276:immunology; D006736:Horses / Q000097:blood*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D012242:Rhodobacter sphaeroides; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D008050:Lipid A; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C049596:diphosphoryl lipid A