title: Differential modulation of the effects of lipopolysaccharide on macrophages by a major outer membrane protein of Proteus mirabilis.
abstract: We previously showed that a major protein isolated from purified cell walls of Proteus mirabilis (39-kDa protein) is a strong modulator of the specific immune responses to LPS from this bacterium in mice. When mixed with LPS before immunization, this protein enhances T cell-dependent, IgG antibody-producing cell responses specific for LPS. Furthermore, complexes of the 39-kDa protein with LPS drastically inhibit the production of oxygen radicals by murine macrophages activated with LPS, as measured in a chemiluminescence assay. In the present report, we have further investigated possible modulating effects of the protein at the level of LPS-macrophage interaction. When mixed with LPS, the 39-kDa protein inhibited IL-1 production by murine macrophages derived from bone marrow in a dose-dependent manner, as determined in an IL-2-dependent IL-1 assay. On the other hand, the protein had little effect on LPS-mediated suppression of MHC class II expression on the surface of macrophages induced with IFN-gamma. Some abrogation of suppression was observed, but the amounts of protein needed for this effect were quite large, in comparison with the amounts rendering inhibition of IL-1 production. In contrast, the 39-kDa protein enhanced the LPS-induced cytotoxicity of macrophages against L929 target cells, primarily as the result of production of TNF. These results show that the 39-kDa protein is a potent modulator of the interaction of LPS with macrophages, exerting its effects in a differential manner with respect to various parameters of LPS-induced activation of macrophages.
authors.affiliation: Department of Microbiology, University of Darmstadt, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Weber
authors.forename: F
authors.initials: F
authors.lastname: Link
authors.forename: E
authors.initials: E
authors.lastname: Ferber
authors.forename: P G
authors.initials: PG
authors.lastname: Munder
authors.forename: D
authors.initials: D
authors.lastname: Zeitter
authors.forename: R R
authors.initials: RR
authors.lastname: Bartlett
authors.forename: K
authors.initials: K
authors.lastname: Nixdorff
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007111:Immunity, Cellular / Q000187:drug effects; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011513:Proteus mirabilis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D001425:Bacterial Outer Membrane Proteins; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha