title: Cytokine response by monocytes and macrophages to free and lipoprotein-bound lipopolysaccharide.
abstract: Recent evidence suggests that bacterial lipopolysaccharide binds to serum lipoproteins in vitro and in vivo and that lipopolysaccharide in the form that is bound to lipoprotein is less biologically active in several experimental models. In order to study the mechanism of this apparent detoxification, we compared the ability of free and lipoprotein-bound lipopolysaccharide from Escherichia coli O18 to stimulate interleukin-1, interleukin-6, and tumor necrosis factor from elicited murine peritoneal macrophages and circulating human monocytes. Lipopolysaccharide bound to lipoprotein was 20- to 1,000-fold less active than the unbound form in inducing the release of each cytokine. We also studied the binding of each form of lipopolysaccharide to the macrophage surface. Lipopolysaccharide complexed to lipoprotein was unable to compete for the binding of radiolabeled heterologous lipopolysaccharide to murine macrophages, and radiolabeled lipopolysaccharide-lipoprotein complexes bound poorly compared with molar equivalents of free lipopolysaccharide. Our experiments suggest that in the process of binding to lipoproteins, lipopolysaccharide may be rendered less toxic through a mechanism of decreased ability to induce monocytes and macrophages to release cytokines, perhaps because of an altered interaction at the cell surface.
authors.affiliation: Unité d'Immuno-Allergie, Institut Pasteur, Paris, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Cavaillon
authors.forename: C
authors.initials: C
authors.lastname: Fitting
authors.forename: N
authors.initials: N
authors.lastname: Haeffner-Cavaillon
authors.forename: S J
authors.initials: SJ
authors.lastname: Kirsch
authors.forename: H S
authors.initials: HS
authors.lastname: Warren
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001685:Biological Factors / Q000096:biosynthesis*; D016207:Cytokines; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology* / Q000378:metabolism; D008074:Lipoproteins / Q000502:physiology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D009345:Neisseria meningitidis / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D001685:Biological Factors; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008074:Lipoproteins; D014409:Tumor Necrosis Factor-alpha