Muramyl dipeptide-Lys stimulates the function of human dendritic cells.
Muramyl dipeptide (MDP)-Lys (L18), a synthetic MDP analogue derived from bacterial cell walls, has been reported to be a potent immunoadjuvant that enhances protective immunity against pathogens and tumors by stimulating immune-competent cells, such as monocytes and macrophages. However, it is not known whether MDP-Lys modulates the function of dendritic cells (DCs), which are the most potent antigen-presenting cells and play a crucial role in initiating T cell-mediated immunity. Therefore, we examined the effects of MDP-Lys on the expression of surface molecules, cytokine production, and antigen-presenting function of human DCs generated from peripheral blood cells in the presence of interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor. We found that MDP-Lys markedly up-regulated the expression of CD80, CD83, CD86, and CD40, but not human leukocyte antigen-DR, and stimulated the production of tumor necrosis factor-alpha, IL-6, IL-8, IL-10, and IL-12 (p40) by human DCs in a dose-dependent manner. Furthermore, MDP-Lys-treated DCs showed enhanced antigen-presenting function compared with untreated DCs, as assessed by an allogeneic mixed lymphocyte reaction. These results suggested that the immunoadjuvant activity of MDP-Lys in vivo is mediated, in part, by its stimulation of DC function.
Todate
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Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
Suda
T
T
Kuwata
H
H
Chida
K
K
Nakamura
H
H
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D017951:Antigen Presentation / Q000187:drug effects; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D005802:Genes, MHC Class II; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006801:Humans; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000494:pharmacology; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D016207:Cytokines; D006684:HLA-DR Antigens; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C036866:romurtide