Abstract
N(2)-[alpha-O-benzyl-N-(acetylmuramyl)-L-alanyl-D-isoglutaminyl]-N(6)-trans-(m-nitrocinnamoyl)-L-lysine (muramyl dipeptide C, or MDP-C) has been synthesized as a novel, nonspecific immunomodulator. The present study shows that MDP-C induces strong cytolytic activity by macrophages on P388 leukemia cells and cytotoxic activity by cytotoxic T lymphocytes (CTLs) on P815 mastocytoma cells. Our results also indicate that MDP-C is an effective stimulator for production of interleukin-2 and interleukin-12 by murine bone marrow derived dendritic cells (BMDCs) and production of interferon-gamma by CTLs. Additionally, MDP-C increases the expression levels of several surface molecules, including CD11c, MHC class I, and intercellular adhesion molecule-1 in BMDCs. Moreover, MDP-C remarkably enhances the immune system's responsiveness to hepatitis B surface antigen (HBsAg) in hepatitis B virus transgenic mice for both antibody production and specific HBsAg T-cell responses ex vivo. Our results indicate that MDP-C is an apyrogenic, nonallergenic, and low-toxicity immunostimulator with great potential for diagnostic, immunotherapeutic, and prophylactic applications in diseases such as hepatitis B and cancers.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylmuramyl-Alanyl-Isoglutamine / adverse effects
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Acetylmuramyl-Alanyl-Isoglutamine / analogs & derivatives*
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Acetylmuramyl-Alanyl-Isoglutamine / chemical synthesis
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Acetylmuramyl-Alanyl-Isoglutamine / pharmacology
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Adjuvants, Immunologic / adverse effects
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Adjuvants, Immunologic / chemical synthesis*
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Adjuvants, Immunologic / pharmacology
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Animals
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Antibody Formation
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Bone Marrow Cells / drug effects
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Bone Marrow Cells / metabolism
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CD11c Antigen / biosynthesis
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Cell Line, Tumor
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Cytotoxicity, Immunologic
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Dendritic Cells / drug effects
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Dendritic Cells / metabolism
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Hepatitis B / immunology
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Hepatitis B Surface Antigens / immunology*
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Hepatitis B Vaccines / immunology
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Histocompatibility Antigens Class I / biosynthesis
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In Vitro Techniques
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Intercellular Adhesion Molecule-1 / biosynthesis
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Interleukin-12 / biosynthesis
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Interleukin-2 / biosynthesis
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Macrophages / drug effects
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Macrophages / immunology
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Rabbits
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Rats
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Rats, Wistar
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T-Lymphocytes, Cytotoxic / drug effects
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T-Lymphocytes, Cytotoxic / immunology
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Toxicity Tests, Acute
Substances
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Adjuvants, Immunologic
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CD11c Antigen
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Hepatitis B Surface Antigens
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Hepatitis B Vaccines
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Histocompatibility Antigens Class I
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Interleukin-2
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N(2)-(O-benzyl-N-(acetylmuramyl)-alanyl-isoglutaminyl)-N(6)-(3-nitrocinnamoyl)-lysine
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Intercellular Adhesion Molecule-1
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Interleukin-12
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Acetylmuramyl-Alanyl-Isoglutamine