Rhizobium sin-1 lipopolysaccharide (LPS) prevents enteric LPS-induced cytokine production.
Endotoxin (lipopolysaccharide (LPS)), a component of Gram-negative bacteria, is among the most potent proinflammatory substances known. The lipid-A region of this molecule initiates the production of multiple host-derived inflammatory mediators, including cytokines (e.g. tumor necrosis factor-alpha (TNFalpha)). It has been a continuous effort to identify methods of interfering with the interaction between enteric LPS and inflammatory cells using natural and synthetic LPS analogs. Some of these LPS analogs (e.g. Rhodobacter spheroides LPS/lipid-A derivatives) are antagonists in human cells but act as potent agonists with cells of other species. Data reported here indicate that structurally novel LPS from symbiotic, nitrogen-fixing bacteria found in association with the root nodules of legumes do not stimulate human monocytes to produce TNFalpha. Furthermore, LPS from one of these symbiotic bacterial species, Rhizobium sp. Sin-1, significantly inhibits the synthesis of TNFalpha by human cells incubated with Escherichia coli LPS. Rhizobium Sin-1 LPS exerts these effects by competing with E. coli LPS for binding to LPS-binding protein and by directly competing with E. coli LPS for binding to human monocytes. Rhizobial lipid-A differs significantly from previously characterized lipid-A analogs in phosphate content, fatty acid acylation patterns, and carbohydrate backbone. These structural differences define the rhizobial lipid-A compounds as a potentially novel class of LPS antagonists that might well serve as therapeutic agents for the treatment of Gram-negative sepsis.
Vandenplas
Michel L
ML
Department of Large Animal Medicine, College of Veterinary Medicine, the University of Georgia, Athens, Georgia 30602, USA. mvdplas@vet.uga.edu
Carlson
Russell W
RW
Jeyaretnam
Benjamin S
BS
McNeill
Brian
B
Barton
Michelle H
MH
Norton
Natalie
N
Murray
Thomas F
TF
Moore
James N
JN
D000209:Acute-Phase Proteins; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D004926:Escherichia coli / Q000472:pathogenicity; D006801:Humans; D008050:Lipid A / Q000737:chemistry / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008562:Membrane Glycoproteins; D012231:Rhizobium / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D008050:Lipid A; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein