A novel immunostimulator, N-[alpha-O-benzyl-N-(acetylmuramyl)-L-alanyl-D-isoglutaminyl]-N6-trans-(m-nitrocinnamoyl)-L-lysine, and its adjuvancy on the hepatitis B surface antigen.
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.
Yang
Hong-Zhen
HZ
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, P. R. China.
Xu
Song
S
Liao
Xue-Yan
XY
Zhang
Suo-De
SD
Liang
Zheng-Lun
ZL
Liu
Bai-He
BH
Bai
Jin-Ye
JY
Jiang
Chao
C
Ding
Jian
J
Cheng
Gui-Fang
GF
Liu
Gang
G
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D039521:CD11c Antigen / Q000096:biosynthesis; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D006509:Hepatitis B / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D023382:Toxicity Tests, Acute
D000276:Adjuvants, Immunologic; D039521:CD11c Antigen; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; C503891:N(2)-(O-benzyl-N-(acetylmuramyl)-alanyl-isoglutaminyl)-N(6)-(3-nitrocinnamoyl)-lysine; D018799:Intercellular Adhesion Molecule-1; D018664:Interleukin-12; D000119:Acetylmuramyl-Alanyl-Isoglutamine