title: Muramyl dipeptide and mononuclear cell supernatant induce Langhans-type cells from human monocytes.
abstract: Muramyl dipeptide (MDP) in bacterial cell walls reportedly evokes epithelioid cell granulomas. We examined its effects on multinucleated-giant-cell (MGC) formation from monocytes. Supernatant of concanavalin A-stimulated peripheral blood mononuclear cells (conditioned medium) generated MGCs from monocytes. MDP significantly increased the fusion index of Langhans-type MGCs (LGCs) but did not affect total MGCs. N-Acetylmuramyl-L-alanyl-L-isoglutamine, an MDP analogue, had no effect on MGC formation. MGCs were produced by conditioned medium from CD14(++)/CD16(-) monocytes. MDP enhanced the LGC fusion index from CD14(++)/CD16(-) monocytes. MGCs were not produced from CD14(+)/CD16(+) monocytes or immature dendritic cells induced by granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL) 4 and only weakly produced from macrophage (M)-CSF- or GM-CSF-induced macrophages. Added MDP did not generate MGCs from CD14(+)/CD16(+) monocytes or dendritic cells but enhanced LGC formation from macrophages. Because IFN-gamma, IL-3, and GM-CSF reportedly are important in LGC induction, we added anti-IFN-gamma, anti-IL-3, or anti-GM-CSF monoclonal antibody (mAb) concomitantly to the monocyte culture treated with conditioned medium alone or plus MDP. Anti-IFN-gamma mAb completely abrogated MGC generation, whereas anti-GM-CSF and anti-IL-3 mAbs significantly inhibited LGCs. These findings suggest that CD14(++)/CD16(-) monocytes are fused to form LGCs by MDP derived from granulomatous-disease-causing pathogens with inflammatory mediators such as IFN-gamma, IL-3, and GM-CSF.
authors.affiliation: Department of Dermatology, Kansai Medical University, Moriguchi, Osaka 570-8507, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Mizuno
authors.forename: H
authors.initials: H
authors.lastname: Okamoto
authors.forename: T
authors.initials: T
authors.lastname: Horio
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D015744:Giant Cells, Langhans / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007377:Interleukin-3 / Q000096:biosynthesis / Q000276:immunology; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis
chemical_list: D000911:Antibodies, Monoclonal; D015214:Antigens, Differentiation, Myelomonocytic; D017077:Culture Media, Conditioned; D007377:Interleukin-3; D018950:Lipopolysaccharide Receptors; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007703:Peptidyl-Dipeptidase A