Protection of mice from lethal endotoxemia by use of an ornithine-containing lipid or a serine-containing lipid.

Abstract

The effects of an ornithine-containing lipid [alpha-N-(3-acyloxyacyl)-ornithine (Orn-L)] or a serine-containing lipid [alpha-N-(3-acyloxyacyl)-serine (Ser-L)] from Flavobacterium meningosepticum on lethal endotoxemia in mice were examined. When 500 micrograms of Orn-L was intravenously administered 1 h before intravenous administration of a lethal dose of endotoxin, none of the mice died. The protective effect of Ser-L was weaker than that of Orn-L. Light and electron microscopic studies demonstrated that necrosis of hepatocytes caused by endotoxin was prevented by pretreatment with Orn-L. Furthermore, Kupffer cells were activated morphologically 1 h after the administration of Orn-L or Ser-L, and the liposomes of the lipoamino acids were incorporated into phagolysosomes in activated Kupffer cells. The activity of tumor necrosis factor in sera of endotoxin-treated mice was decreased markedly by pretreatment of mice with Orn-L. In vitro, the lipoamino acids suppressed endotoxin-induced tumor necrosis factor generation but did not suppress tumor necrosis factor generation induced by zymosan and whole cells of Staphylococcus aureus. These results suggested that Orn-L and Ser-L can be used as specific blocking agents against endotoxin. The blocking mechanism may be antagonistic, because of the structural similarities between the lipoamino acids and endotoxin lipid A.

• Authors: Y Kawai, K Kaneda, Y Morisawa, K Akagawa
• Journal: Infection and immunity (Infect Immun) Vol. 59 Issue 8 Pg. 2560-6 (Aug 1991) ISSN: 0019-9567 [Print] United States
• PMID: 1906840 (Publication Type: Journal Article)

Chemical References

• Lipids
• Lipopolysaccharides
• Tumor Necrosis Factor-alpha
• ornithine containing aminolipid
• serine containing aminolipid
• Serine
• Ornithine

Topics

• Animals
• Cell Line
• Flavobacterium (analysis)
• Lipids (isolation & purification, pharmacology, toxicity)
• Lipopolysaccharides (administration & dosage, antagonists & inhibitors)
• Liver (pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred ICR
• Microscopy, Electron
• Ornithine (analogs & derivatives, isolation & purification, pharmacology, toxicity)
• Serine (analogs & derivatives, isolation & purification, pharmacology, toxicity)
• Shock, Septic (prevention & control)
• Tumor Necrosis Factor-alpha (metabolism)