Dissociation of cell-associated interleukin-1 (IL-1) and IL-1 release induced by lipopolysaccharide and lipid A.
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.
Cavaillon
J M
JM
Unité d'Immuno-Allergie, Institut Pasteur, Paris, France.
Fitting
C
C
Caroff
M
M
Haeffner-Cavaillon
N
N
D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology; D001681:Biological Assay; D001886:Bordetella pertussis; D002462:Cell Membrane / Q000378:metabolism; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism*; D008050:Lipid A / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D012636:Secretory Rate / Q000187:drug effects
D007375:Interleukin-1; D008050:Lipid A; D008070:Lipopolysaccharides