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

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670313/
• 关键词: phagocytosis; phago-lysosomefusion; virulence factor; glycopeptido lipid; cord-factor; serotype-4 GPL; Mycobacterium auium; M.tuberculosis; ファゴ・リソゾーム融合; M.tuberculosis; 結核菌; ファゴソーム・リソゾーム融合; グリコペプチドリピド; スルホリピッド; 食細胞機能阻害

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.

分枝杆菌复合物（MAC）是与HIV（AIDS）和典型的细胞内寄生虫以及大麻结核的最重要的病原体之一。还集中的是，疗法感染会引起免疫抑制，尤其是在宿主动物的细胞免疫中，而特定的血清型 - 异种（如血清型-2，-4 OR-8）可以在AIDS中经常在人类感染中分离出来。Furthermore，感染后的预后因血清型差异。 Sero-4通常显示出重型感染，而Sero-16显示出快速改善。因此，我们对表面糖肽（GPL）抗原的免疫化活性感兴趣。但是，迄今为止，尚无关于直接与细胞内细菌杀死直接相关的MAC的有毒因素的信息。最近，我们试图测试从MAC复合物中纯化的各种GPL对人外围血单核细胞（PBMC）的吞噬过程的影响。我们已经使用了GPL涂层的热杀死的葡萄球菌细胞被PBMC吞噬，并通过融合囊泡和细菌的acridine橙色染色来估算P-L融合。结果，血清型-4 GPL表现出强烈的吞噬作用促进并明显抑制P-L融合，而血清型16 GPL既没有促进吞噬作用，也没有抑制吞噬细胞中P-L融合的抑制作用。血清型-8 GPL同时刺激了吞噬作用和P-L融合。这些影响可能是由于特定碳水化合物链和有机埃膜之间的未知相互作用所致，而血清型-4 GPL可能是人吞噬细胞中MAC感染的可能有毒因素之一。将报道与已知可能的有毒因子（例如绳索因子，海藻糖单霉菌酸盐或磺胺脂）进行比较。

项目成果

Seiko Yamaguchi: "Stimulatory effect of gangliosides on phagocytosis,phagosome-lysosome fusion,and intracellular signal transduction system by human polymophonuclear leukocytes" Glycoconjugate Journal. 14. 707-714 (1997)

Seiko Yamaguchi：“神经节苷脂对人多形核白细胞吞噬作用、吞噬体-溶酶体融合和细胞内信号转导系统的刺激作用”糖复合物杂志。

Yoshiko Miyazaki et al.: "Stimulation of phagocytosis and phagosome-Lysosome fusion by Glycosphingolopids from Sphingomonas paucimobilis" J.Biochem.118. 271-277 (1995)

Yoshiko Miyazaki 等人：“少动鞘氨醇鞘糖脂对吞噬作用和吞噬体-溶酶体融合的刺激”J.Biochem.118。

Seiko Yamaguchi: "Stimulatory effect of gangliosides on phagocytosis,phagosome-lysosome fusion,and intracellular signal transduction system by human polymorphonuclear leukocytes" Glycoconjugate Journal. 14. 707-714 (1997)

Seiko Yamaguchi：“神经节苷脂对人多形核白细胞吞噬作用、吞噬体-溶酶体融合和细胞内信号转导系统的刺激作用”糖复合物杂志。

Seiko Yamaguchi et al.: "Stimulation of phagocytosis and phagosome-lysosome (P-L) fusion of human polymorphonuclear leukocytes by sulfatide (galactosylceramide-3-sulfate)" FEMS Immunology and Medical Microbiology. 13. 107-111 (1996)

Seiko Yamaguchi 等人：“硫脑苷脂（半乳糖神经酰胺-3-硫酸酯）对人多形核白细胞的吞噬作用和吞噬体-溶酶体 (P-L) 融合的刺激”FEMS 免疫学和医学微生物学。

藤原 永年: "人型結核菌株間における抗原性糖脂質の分布とvirulenceへの寄与に関する研究" 結核. 72No.4. 21-33 (1997)

Eitoshi Fujiwara：“结核分枝杆菌菌株中抗原糖脂的分布及其对毒力的贡献的研究”Tuberculosis 72No.4（1997）。