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Rhizobium sin-1 LPS prevents enteric LPS-induced cytokine production by mono Mac 6 cells

Abstract

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., TNF). 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 sphaeroides 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 TNF. Further, LPS from one of these symbiotic bacterial species, Rhizobium sp. Sin-1 (R. Sin-1), significantly inhibits the synthesis of TNFnby human cells incubated with E. coli LPS. R. 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.

Authors: Vandenplas ML, Carlson RW, Jeyaretnam BS, McNeill B, Barton MH, Norton N, Murray TF, Moore JN
Journal: J Biol Chem 277: 41811-41816
Year: 2002
PubMed: Find in PubMed