Inhibition of endotoxin-induced priming of human neutrophils by lipid X and 3-Aza-lipid X.

Abstract

Lipid X, a precursor of lipid A (the toxic moiety of endotoxin), has been shown to protect animals from the lethal effects of endotoxin challenge. We investigated the mechanism of action of lipid X and 3-aza-lipid X, a diamino-analogue, in vitro, using the ability of lipopolysaccharide (LPS) to prime neutrophils for an enhanced release of toxic oxygen radicals. Lipid X and 3-aza-lipid X inhibited LPS-induced neutrophil priming in a concentration-dependent manner. At high concentrations, 3-aza-lipid X was a partial agonist of priming. Lipid X was found to inhibit LPS-induced priming by directly interacting with the neutrophil in contrast to polymyxin B, which neutralized LPS by binding to it. Increasing concentrations of lipid X shifted the LPS dose response curve of neutrophils rightward but did not prevent maximum priming at higher LPS concentrations, a finding consistent with competitive inhibition. These results suggest that lipid X, a compound structurally related to lipid A, may block neutrophil priming by competing with LPS for cellular binding sites. Lipid X appears to have a novel mechanism of inhibiting LPS effect and may have efficacy in the treatment of gram-negative sepsis.

• Authors: R L Danner, K A Joiner, J E Parrillo
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 80 Issue 3 Pg. 605-12 (Sep 1987) ISSN: 0021-9738 [Print] United States
• PMID: 3624479 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Endotoxins
• Glycolipids
• Lipopolysaccharides
• 3-aza-lipid X
• lipid X

Topics

• Dose-Response Relationship, Drug
• Endotoxins (antagonists & inhibitors, pharmacology)
• Glycolipids (pharmacology)
• Humans
• Lipopolysaccharides (antagonists & inhibitors, pharmacology)
• Neutrophils (drug effects)
• Osmolar Concentration
• Salmonella