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（Mycobacterium avium complex， MAC）是与HIV （AIDS）共感染的重要病原体之一，是一种典型的细胞内寄生虫，与结核分枝杆菌一样。人们还注意到，鸟分枝杆菌感染引起免疫抑制，特别是在宿主动物的细胞免疫中，并且在艾滋病人感染中经常可以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；血清-4一般显示严重感染，而血清-16显示迅速改善。因此，我们对表面糖肽类脂（GPL）抗原的免疫修饰活性非常感兴趣。然而，到目前为止，还没有关于MAC的毒力因子与细胞内细菌杀伤直接相关的信息。最近，我们试图测试从MAC复合物中纯化的各种GPLs对人外周血单核细胞（PBMC）吞噬过程的影响。我们用gpl包被的热杀葡萄球菌细胞被PBMC吞噬，并通过融合囊泡和细菌的吖啶橙染色来估计P-L融合。结果表明，血清型GPL 4对吞噬细胞有较强的促进作用，对P-L融合有明显的抑制作用，而血清型GPL 16对吞噬细胞的吞噬作用没有促进作用，对P-L融合没有抑制作用。血清8型GPL同时表现出吞噬和P-L融合的刺激。这些影响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，血清型4 GPL可能是人吞噬细胞感染MAC的可能毒力因素之一。将报告与已知的可能致毒因子如脐带因子、海藻糖单菌酸盐或磺胺类进行比较。

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.