title: Preexposure of mouse peritoneal macrophages to lipopolysaccharide and other stimuli enhances the nitric oxide response to secondary stimuli.
abstract: The aim of this study was to compare the regulation of the production of tumor necrosis factor-alpha (TNF-alpha) and secondary nitric oxide (NO) in macrophages submitted to a sequence of two stimulations. Pre-exposure for 18 h of mouse thioglycollate-elicited peritoneal macrophages to low doses (1-10 ng/ml) of lipopolysaccharide (LPS), in the presence or absence of serum, induces on one hand a desensitization (endotoxin tolerance) for secondary TNF-alpha responses to LPS and, on the other hand, a 4 fold increase (priming) of secondary NO responses. Preexposure to components from Gram-positive bacteria (lipoteichoic acid, peptidoglycan) and to a synthetic lipid structurally related to lipid A (compound M4), induced similar effects. In contrast to the desensitization for TNF-alpha secretion, the priming for NO production was not mimicked by sodium nitroprusside, a generator of NO. The results suggest that concomitant but distinct activation pathways induced by LPS and other agents can be dissociated by serum-independent modulation processes elicited by pre-exposure of the cells to LPS itself, or to other stimuli.
authors.affiliation: URA-1116 du C.N.R.S., Université de Paris-Sud, Orsay, France.
authors.forename: H
authors.initials: H
authors.lastname: Fahmi
authors.forename: P
authors.initials: P
authors.lastname: Ancuta
authors.forename: S
authors.initials: S
authors.lastname: Perrier
authors.forename: R
authors.initials: R
authors.lastname: Chaby
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D018950:Lipopolysaccharide Receptors / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D010457:Peptidoglycan / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016895:Culture Media, Serum-Free; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide