A glycolipid precursor of bacterial lipopolysaccharide (lipid X) lacks activity against endothelial cells in vitro and is not toxic in vivo.
Lipid X (2,3-diacylglucosamine-1-phosphate) accumulates in mutants of Escherichia coli incapable of assembling the disaccharide backbone of lipid A, the principle endotoxic moiety of bacterial lipopolysaccharide (LPS). We compared the effects of lipid X on cultured bovine aortic endothelial cell (BEC) viability and prostacyclin (PGI2) release with those of lipid A and LPS. At 10(-5) M, both LPS and lipid A produced significant BEC cytotoxicity (percentage cytotoxicity 69 +/- 4 for LPS and 51 +/- 11 for lipid A) and induced a variable but consistent increase in the release of PGI2 (11- to 73-fold increase for LPS and 4- to 6-fold increase for lipid A). Lipid X, in contrast, was not toxic and did not induce PGI2 release at 10(-4) M. Pretreatment and coincubation of BEC with lipid X, at a concentration 100 times greater than LPS, failed to prevent LPS-mediated cytotoxicity. Intravenous infusion of lipid X in goats had no effect except for a modest elevation in the pulmonary artery pressure during the period of infusion. Moreover, pretreatment of goats with lipid X (70 micrograms/kg) did not block the effects of a subsequent infusion of LPS (5 micrograms/kg). These data suggest that a fatty acid-substituted disaccharide is the minimal molecular requirement for the numerous effects in vivo and activity in vitro induced by LPS. Furthermore, these effects are not prevented by pretreatment with a monosaccharide precursor of lipopolysaccharide, lipid X, at a dose 10- to 100-fold greater than that of LPS.
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis / Q000096:biosynthesis; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004926:Escherichia coli; D006017:Glycolipids / Q000494:pharmacology* / Q000633:toxicity; D006041:Goats; D007958:Leukocyte Count; D008033:Limulus Test; D008050:Lipid A / Q000494:pharmacology* / Q000633:toxicity; D008070:Lipopolysaccharides / Q000494:pharmacology / Q000633:toxicity; D011863:Radioimmunoassay; D014734:Vibrio cholerae
D006017:Glycolipids; D008050:Lipid A; D008070:Lipopolysaccharides; D015121:6-Ketoprostaglandin F1 alpha; C044283:lipid X