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

R. L. Danner, K. A. Joiner, J. E. Parrillo

Research output: Contribution to journalArticle

41 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)605-612
Number of pages8
JournalJournal of Clinical Investigation
Volume80
Issue number3
DOIs
StatePublished - Jan 1 1987
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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