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(Journal of Leukocyte Biology. 2001;70:386-394.)
© 2001 by Society for Leukocyte Biology

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

Department of Dermatology, Kansai Medical University, Moriguchi, Osaka 570-8507, Japan

Correspondence: Hiroyuki Okamoto, MD, Department of Dermatology, Kansai Medical University, 10-15 Fumizono, Moriguchi, Osaka 570-8507, Japan. E-mail: hokamoto{at}takii.kmu.ac.jp

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-, IL-3, and GM-CSF reportedly are important in LGC induction, we added anti-IFN-, 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- 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-, IL-3, and GM-CSF.

Key Words: CD14^++/CD16^- monocytes • granuloma • macrophages • dendritic cells

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