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PROMOTION OF PHAGOCYTOSIS AND PREVENTION OF PHAGOSOME-LYSOSOME (P-L) FUSION IN HUMAN PERIPHERAL BLOOD MONOCYTES BY SEROTYPE SPECIFIC GLYCOPEPTIDOLIPID (GPL) ANTIGEN OF MYCOBACTERIUM AVIUM COMPLEX (MAC)

鸟分枝杆菌复合体 (MAC) 血清型特异性糖肽脂 (GPL) 抗原促进人外周血单核细胞的吞噬作用并预防吞噬体-溶酶体 (P-L) 融合

基本信息

批准号：
08670313
负责人：
TANO Ikuya
金额：
$ 1.02万
依托单位：
OSAKA CITY UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

Mycobacterium avium complex (MAC) is one of the most important pathogen coinfected with HIV (AIDS) and a typical intracellular parasite as well as M.tuberculosis. It is also focused that M.avium infection causes immunosuppression especially in the cellular immunity of host animals, and specific serotype-subspecies such as serotype-2, -4 or-8 can be isolated frequently in human infection in AIDS.Furthermore, the prognosis after infection differs by the serotype ; sero-4 shows heavy infection in general, while sero-16 shows rapid improvement. Therefore, we have been interested in the immunomodifying activity of surface glycopeptidolipid (GPL) antigen. However, to date, no information has been available on the virulent factor of MAC related directly with intracellular bacterial killing. Recently, we have tried to test the effect of various GPLs purified from MAC complex on phagocytic processes of human peripferal blood monocytes (PBMC). We have used GPL-coated heat-killed staphylococcal cells to be phagocytosed by PBMC,and P-L fusion was estimated by the acridine orange staining of fused vesicles and bacteria. As the results, serotype-4 GPL showed strong phagocytosis promotion and marked inhibition of P-L fusion, while serotype-16 GPL showed neither promotion of phagocytosis, nor inhibition of P-L fusion in phagocytic cells. Serotype-8 GPL showed stimulation of both phagocytosis and P-L fusion, concomitantly. These effects may be due to unknown interaction between specific carbohydrate chain and organella membranes, and serotype-4 GPL may be one of the possible virulent factors in MAC infection in human phagocytic cells. Comparison with known possible virulent factors such as cord factor, trehalose monomycolate or sulfolipids will be reported.

鸟分枝杆菌复合体（Mycobacterium avium complex，MAC）是HIV（AIDS）的重要病原体之一，与结核分枝杆菌一样是典型的胞内寄生虫。禽支原体感染引起免疫抑制，尤其是宿主动物的细胞免疫抑制，并且在人类感染AIDS中经常可以分离到特定的血清型-亚种，例如血清型-2、-4或-8。此外，感染后的预后因血清型而异;血清型-4通常显示重度感染，而血清型-16显示快速改善。因此，我们一直对表面糖肽脂（GPL）抗原的免疫调节活性感兴趣。然而，迄今为止，没有关于MAC的毒力因子与细胞内细菌杀灭直接相关的信息。最近，我们试图测试从MAC复合物中纯化的各种GPL对人外周血单核细胞（PBMC）吞噬过程的影响。我们使用GPL包被的热灭活的葡萄球菌细胞被PBMC吞噬，并通过融合囊泡和细菌的吖啶橙子染色来评估P-L融合。结果表明，血清4型GPL对吞噬细胞的吞噬功能有明显的促进作用，对P-L融合有明显的抑制作用，而血清16型GPL对吞噬细胞的吞噬功能无促进作用，对P-L融合无抑制作用。血清型-8 GPL显示同时刺激吞噬作用和P-L融合。这些效应可能是由于特定的糖链和细胞器膜之间的未知相互作用，血清型-4 GPL可能是MAC感染人吞噬细胞的可能毒力因子之一。将报告与已知可能的毒力因子（如脐带因子、海藻糖单霉菌酸酯或硫脂）的比较。