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[结核杆菌各组分的生化及免疫学特性]

[Biochemical and immunological properties of the fractions of tubercle bacilli].

作者信息

Azuma I

机构信息

Institute of Immunological Science Hokkaido University, Sapporo, Japan.

出版信息

Kekkaku. 1998 Feb;73(2):65-70.

PMID:9545698
Abstract

In 1954, Dr. Yuichi Yamamura and his coassociates, National Sanatorium Toneyama Hospital, has reported the formation of experimental tuberculous cavity in rabbits. This work was a milestone of the researches in the field of cellular immunology. In 1960, I have started my scientific carrier in Kyushu University Medical School as the post-graduate student under the guidance of Prof. Yamamura. Since then, I have worked on the field of biochemical and immunological properties of tubercle bacilli. The arabinose mycolate, polysaccharides, cell-wall skeleton (CWS) and trehalose dimycolate (TDM) were purified from tubercle bacilli and their Chemical structures and biological activities were investigated in detail in our laboratory. In 1971, we have reported that adjuvant active principle of tubercle bacilli was a CWS fraction, and the details of chemical structure and adjuvantity of mycobacterial CWS were investigated in our research group. The application of BCG-CWS to cancer immunotherapy was also studied. In 1974, Prof. E. Lederer and his coworkers, University of Paris, have reported that N-acetyl muramyl-L-alanyl-D-isoglutamine (MDP) was the minimum adjuvant-active structure of bacterial cell wall. We have synthesized several hundreds of MDP derivatives and selected, MDP-Lys(L18), romurtide, as the candidate of cytokine inducer for the clinical application. Romurtide is applied in cancer patients for the recovery of the number and functions of monocytes, neutrophils and platelets. These results suggest that the tubercle bacilli, especially, CWS and related synthetic MDP derivatives, are effective for the potentiation of host resistance against infectious diseases and cancer.

摘要

1954年,丰山国立疗养院医院的山村雄一医生及其同事报告了在兔子身上形成实验性结核空洞的情况。这项工作是细胞免疫学领域研究的一个里程碑。1960年,我作为研究生在山村教授的指导下开始了在九州大学医学院的科研生涯。从那时起,我一直致力于结核杆菌的生化和免疫学特性研究。从结核杆菌中纯化出阿拉伯糖霉菌酸、多糖、细胞壁骨架(CWS)和海藻糖二霉菌酸(TDM),并在我们实验室详细研究了它们的化学结构和生物学活性。1971年,我们报告结核杆菌的佐剂活性成分是CWS部分,并在我们的研究小组中研究了分枝杆菌CWS的化学结构和佐剂活性的细节。还研究了卡介苗细胞壁骨架在癌症免疫治疗中的应用。1974年,巴黎大学的E. 勒德雷尔教授及其同事报告说,N-乙酰胞壁酰-L-丙氨酰-D-异谷氨酰胺(MDP)是细菌细胞壁的最小佐剂活性结构。我们合成了数百种MDP衍生物,并选择MDP-Lys(L18)即罗慕肽作为临床应用的细胞因子诱导剂候选物。罗慕肽用于癌症患者以恢复单核细胞、中性粒细胞和血小板的数量及功能。这些结果表明结核杆菌,特别是CWS和相关的合成MDP衍生物,对增强宿主抵抗传染病和癌症的能力有效。

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