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.

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.
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一种新型免疫刺激剂N-[α-O-苄基-N-(乙酰胞壁酰)-L-丙氨酰-D-异谷氨酰胺酰]-N6-反式-(间硝基肉桂酰)-L-赖氨酸及其在乙型肝炎表面的佐剂

DOI:
10.1021/jm0493313
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发表时间:
2005
影响因子:
7.3
通讯作者:
Liu,Gang
Liu,Gang
中科院分区:
医学1区
文献类型:
--
作者:
Yang,Hong-Zhen;Xu,Song;Liao,Xue-Yan;Zhang,Suo-De;Liang,Zheng-Lun;Liu,Bai-He;Bai,Jin-Ye;Jiang,Chao;Ding,Jian;Cheng,Gui-Fang;Liu,Gang

文献摘要

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N_2-[α-O-苄基-N-(乙酰胞壁酰)-l-丙氨酰-d-异谷氨酰]-N_6-反式-(间硝基肉桂酰)-l-赖氨酸(胞壁酰二肽C,或MDP-C)是一种新型的非特异性免疫调节剂。目前的研究表明,MDP-C诱导强的细胞溶解活性的巨噬细胞对P388白血病细胞和细胞毒性T淋巴细胞(CTL)对P815肥大细胞瘤细胞的细胞毒活性。MDP-C对小鼠骨髓来源的树突状细胞(BMDCs)产生白细胞介素-2(IL-2)和白细胞介素-12(IL-12)以及CTL产生γ-干扰素(IFN-γ)具有明显的刺激作用。此外,MDP-C增加了几种表面分子的表达水平,包括BMDC中的CD 11 c、MHC I类和细胞间粘附分子-1。此外,MDP-C显著增强了免疫系统对B型肝炎病毒转基因小鼠中的B型肝炎表面抗原(HBsAg)的应答,以产生抗体和特异性HBsAg T细胞离体应答。我们的研究结果表明,MDP-C是一种无热原,无过敏性,低毒性的免疫刺激剂,在诊断,免疫和预防疾病,如B型肝炎和癌症的应用有很大的潜力。
N2-[α-O-Benzyl-N-(acetylmuramyl)-l-alanyl-d-isoglutaminyl]-N6-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 morrow derived dendritic cells (BMDCs) and production of interferon-γ 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.