Muramyl dipeptide and mononuclear cell supernatant induce Langhans-type cells from human monocytes

Muramyl dipeptide (MDP) in bacterial cell walls reportedly evokes epithelio id cell granulomas. We examined its effects on multinucleated-giant-cell (M GC) formation from monocytes. Supernatant of concanavalin A-stimulated peri pheral blood mononuclear cells (conditioned medium) generated MGCs from mon ocytes. MDP significantly increased the fusion index of Langhans-type MGCs (LGCs) but did not affect total MGCs. N-Acetylmuramyl-L-alanyl-L-isoglutami ne, an MDP analogue, had no effect on MGC formation. MGCs were produced by conditioned medium from CD14(++)/CD16(-) monocytes. MDP enhanced the LGC fu sion index from CD14++/CD16- monocytes. MGCs were not produced from CD14(+) / CD16(+) monocytes or immature dendritic cells induced by granulocyte macr ophage-colony stimulating factor (GM-CSF) and interleukin (IL) 4 and only w eakly produced from macrophage (M)-CSF- or GM-CSF-induced macrophages. Adde d MDP did not generate MGCs from CD14(+)/CD16(+) monocytes or dendritic cel ls but enhanced LGC formation from macrophages. Because IFN-gamma, IL-3, an d GM-CSF reportedly are important in LGC induction, we added anti-IFN-gamma , anti-IL-3, or anti-GMCSF monoclonal antibody (mAb) concomitantly to the m onocyte culture treated with conditioned medium alone or plus MDP. Anti-IFN -gamma mAb completely abrogated MGC generation, whereas anti-GM-CSF and ant i-IL-3 mAbs significantly inhibited LGCs. These findings suggest that CD14( ++)/CD16(-) monocytes are fused to form LGCs by MDP derived from granulomat ous-disease-causing pathogens with inflammatory mediators such as IFN-gamma , IL-3, and GM-CSF.