Protection of mice against lethal endotoxemia by lipid X is mediated through inhibition of neutrophil function.

Abstract

The effects of lipid X and 3-aza-lipid X on in vitro neutrophil function were related to their ability to inhibit the toxicity of endotoxin in galactosamine-sensitized mice. In vitro, lipid X and 3-aza-lipid X (100 ng/ml) blocked completely endotoxin (100 ng/ml)-enhanced neutrophil aggregation, superoxide anion generation, and release of beta-glucuronidase in response to a chemotactic tripeptide, f-met-leu-phe (10(-7) M). In vivo, lipid X at 250 micrograms/mouse (but not 3-aza-lipid X at a similar dose) protected groups of 10 mice from an otherwise lethal dose of endotoxin in galactosamine-sensitized mice when it was administered IV 4 hr or 2 hr before endotoxin challenge. The minimum effective dose of lipid X that could protect 50% of the challenged mice was calculated to be 715 micrograms/kg. However, lipid X failed to suppress neutrophil infiltration into the lungs. The ability of lipid X to inhibit endotoxin-induced neutrophil responses and to protect against lethal endotoxemia may be due to induction of early phase tolerance to endotoxin by the compound.

• Authors: C Lam, E Schütze, H Walzl, E Basalka
• Journal: Circulatory shock (Circ Shock) Vol. 22 Issue 4 Pg. 311-21 ( 1987) ISSN: 0092-6213 [Print] United States
• PMID: 2820606 (Publication Type: Journal Article)

Chemical References

• Glycolipids
• Lipid A
• Lipopolysaccharides
• 3-aza-lipid X
• Superoxides
• Galactosamine
• lipid X
• Glucuronidase

Topics

• Animals
• Cell Aggregation (drug effects)
• Galactosamine
• Glucuronidase (blood)
• Glycolipids (pharmacology)
• Humans
• In Vitro Techniques
• Lipid A (pharmacology)
• Lipopolysaccharides (antagonists & inhibitors)
• Lung Diseases (etiology, prevention & control)
• Male
• Mice
• Mice, Inbred C57BL
• Neutrophils (drug effects, enzymology)
• Shock, Septic (complications, prevention & control)
• Superoxides (blood)