Dissociation of Cell-Associated interleukin-1 (IL-1) and IL-1 Release Induced by Lipopolysaccharide and Lipid A

Infect Immun. 1989 Mar;57(3):791-7.

Abstract

The capacities of lipopolysaccharide (LPS) and lipid A to trigger mouse BALB/c peritoneal macrophages and to induce the production of cell-associated interleukin-1 (IL-1) and membrane-associated IL-1 and IL-1 release have been compared. Bordetella pertussis lipid A was 1,000 to 10,000 times less efficient than the native LPS to induce IL-1 release by freshly isolated elicited macrophages. When resident macrophages were studied, lipid A, at high concentrations (greater than 2 micrograms/ml), induced significant levels of cell-associated IL-1 but little or no IL-1 release. With synthetic lipid A built up with the Escherichia coli lipid A structure (compound 506), IL-1 activity was present in the supernatants of elicited peritoneal macrophages and to a lesser extent in those of resident macrophages. However, the release of IL-1 induced by synthetic lipid A 506 remained much lower than those induced by rough LPS. Membrane-associated IL-1 could be induced on BALB/c macrophages with LPS and natural or synthetic lipid A, the LPS being the most active. In C3H/HeJ mice, neither natural nor synthetic lipid A could induce detectable cell-associated IL-1, whereas LPS could induce cell-associated and membrane IL-1 activity but no IL-1 release. Our results indicate that fragments of endotoxins may induce the production of IL-1 but the entire structure of the LPS molecule is the most effective to induce intracellular IL-1 production, expression of membrane IL-1, and release of IL-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascitic Fluid / cytology
  • Biological Assay
  • Bordetella pertussis
  • Cell Membrane / metabolism
  • In Vitro Techniques
  • Interleukin-1 / metabolism*
  • Lipid A / pharmacology*
  • Lipopolysaccharides / pharmacology*
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred Strains
  • Secretory Rate / drug effects

Substances

  • Interleukin-1
  • Lipid A
  • Lipopolysaccharides