Muramyl dipeptide-Lys stimulates the function of human dendritic cells.

Abstract

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.

• Authors: A Todate, T Suda, H Kuwata, K Chida, H Nakamura
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 70 Issue 5 Pg. 723-9 (Nov 2001) ISSN: 0741-5400 [Print] United States
• PMID: 11698491 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Antigens, CD
• Cytokines
• HLA-DR Antigens
• Interleukins
• Tumor Necrosis Factor-alpha
• Interleukin-4
• Acetylmuramyl-Alanyl-Isoglutamine
• Granulocyte-Macrophage Colony-Stimulating Factor
• romurtide

Topics

• Acetylmuramyl-Alanyl-Isoglutamine (analogs & derivatives, pharmacology)
• Adjuvants, Immunologic (pharmacology)
• Antigen Presentation (drug effects)
• Antigens, CD (biosynthesis, genetics)
• Cells, Cultured (drug effects)
• Cytokines (biosynthesis, genetics)
• Dendritic Cells (cytology, drug effects, immunology, metabolism)
• Dose-Response Relationship, Drug
• Gene Expression Regulation (drug effects)
• Genes, MHC Class II
• Granulocyte-Macrophage Colony-Stimulating Factor (pharmacology)
• HLA-DR Antigens (biosynthesis)
• Humans
• Immunophenotyping
• Interleukin-4 (pharmacology)
• Interleukins (biosynthesis, genetics)
• Lymphocyte Activation
• T-Lymphocytes (immunology)
• Tumor Necrosis Factor-alpha (biosynthesis, genetics)