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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（MAC）是与艾滋病毒（AIDS）共同感染的最重要的病原体之一，也是一种典型的细胞内寄生虫，与结核分枝杆菌一样。值得关注的是，鸟分枝杆菌感染引起免疫抑制，尤其是宿主动物的细胞免疫，在人类艾滋病感染中经常分离到特定的血清型亚种，如血清型2、-4或-8。此外，感染后的预后因血清型而异； sero-4总体上表现出严重感染，而sero-16表现出快速改善。因此，我们对表面糖肽脂（GPL）抗原的免疫调节活性很感兴趣。然而，迄今为止，还没有关于与细胞内细菌杀灭直接相关的MAC毒力因子的信息。最近，我们尝试测试从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包被的热灭活葡萄球菌细胞进行PBMC的吞噬，并通过融合囊泡和细菌的吖啶橙染色来评估P-L融合。结果，血清型4 GPL在吞噬细胞中表现出强烈的吞噬作用促进作用和显着的P-L融合抑制作用，而血清型16 GPL既不促进吞噬作用，也不抑制吞噬细胞中的P-L融合作用。血清型 8 GPL 同时显示出对吞噬作用和 P-L 融合的刺激。这些效应可能是由于特定碳水化合物链和细胞器膜之间未知的相互作用所致，血清型4 GPL可能是人吞噬细胞MAC感染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、海藻糖单菌酸酯或硫脂）的比较。