Succinylated lipid A is a potent and specific inhibitor of endotoxin mitogenicity

J Gen Microbiol. 1992 Dec;138(12):2503-8. doi: 10.1099/00221287-138-12-2503.

Abstract

Chemically modified lipopolysaccharides of Salmonella abortus-equi were tested for mitogenicity on mouse spleen cells as well as antagonism of the mitogenicity of intact lipopolysaccharide (LPS). All the lipopolysaccharide preparations deacylated by different alkaline treatments suffered a drastic loss of mitogenicity. The mitogenic activity of lipid A was also lost when succinic residues were introduced on hydroxyl groups. Partially deacylated alkaline-treated preparations (but not completely deacylated preparations) inhibited the activation of splenic B-cells by LPS. They were found to be toxic to spleen cells, however, and to suppress not only the mitogenicity of LPS but that of concanavalin A as well. This inhibitory action was not exhibited when all of the fatty acid was eliminated. Succinylated lipid A, on the other hand, was not toxic to the cells and inhibited the B-cell mitogenicity of lipopolysaccharide (but not the T-cell mitogenicity of concanavalin A). Chemical analysis revealed that about 4.6 mol of succinic acid had been introduced into lipid A by succinylation, and that the fatty acid and phosphate composition was unchanged by this treatment. Macrophages do not seem to participate in this inhibition. Inhibition was observed when succinylated lipid A was added either at the same time or after lipid A mitogen, but optimal inhibition was expressed when it was added to the culture 3 h before LPS. Inhibition was not affected by washing the cells before adding LPS. Inhibition increased as the ratio of suppressor to mitogen increased, suggesting that the succinylated lipid A competes with intact LPS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • Cell Death / drug effects
  • Cell Division / drug effects
  • Concanavalin A / pharmacology
  • Dose-Response Relationship, Drug
  • Fatty Acids / analysis
  • Female
  • Lipid A / analogs & derivatives*
  • Lipid A / pharmacology*
  • Lipopolysaccharides / chemistry
  • Lipopolysaccharides / pharmacology*
  • Lymphocyte Activation / drug effects*
  • Mice
  • Mice, Inbred BALB C
  • Mitogens / antagonists & inhibitors*
  • Salmonella / chemistry
  • Spleen / cytology
  • Spleen / drug effects*

Substances

  • Fatty Acids
  • Lipid A
  • Lipopolysaccharides
  • Mitogens
  • succinyl lipid A
  • Concanavalin A