Nigou J, Gilleron M, Cahuzac B, Bounéry J D, Herold M, Thurnher M, Puzo G
Institut de Pharmacologie et de Biologie Structurale du Centre National de la Recherche Scientifique, 118 route de Narbonne, 31062 Toulouse Cedex, France.
J Biol Chem. 1997 Sep 12;272(37):23094-103. doi: 10.1074/jbc.272.37.23094.
Lipoarabinomannans are major mycobacterial antigens capable of modulating the host immune response; however, the molecular basis underlying the diversity of their immunological properties remain an open question. In this study a new extraction and purification approach was successfully applied to isolate ManLAMs (lipoarabinomannans with mannosyl extensions) from bacillus Calmette Guérin leading to the obtention of two types of ManLAMs namely parietal and cellular. Structurally, they were found to differ by the percentage of mannooligosaccharide caps, 76 and 48%, respectively, and also, thanks to a new analytical method, by the structure of the phosphatidyl-myo-inositol anchor lipid moiety. A novel fatty acid in the mycobacterium genus assigned to a 12-O-(methoxypropanoyl)-12-hydroxystearic acid was the only fatty acid esterifying C-1 of the glycerol residue of the parietal ManLAMs, while the phosphatidyl unit of the cellular ManLAMs showed a large heterogeneity due to a combination of palmitic and tuberculostearic acid. Finally, parietal and cellular ManLAMs were found to differentially affect interleukin-8 and tumor necrosis factor-alpha secretion from human dendritic cells. We show that parietal but not cellular ManLAMs were able to stimulate tumor necrosis factor-alpha secretion from dendritic cells. From these studies we propose that the 1-[12-O-(methoxypropanoyl)-12-hydroxystearoyl]-sn-glycerol part is the major cytokine-regulating component of the ManLAMs. It seems likely that modification of the ManLAM lipid part, which may occur in hostile environments, could regulate macrophagic mycobacterial survival by altering cytokine stimulation.
脂阿拉伯甘露聚糖是能够调节宿主免疫反应的主要分枝杆菌抗原；然而，其免疫特性多样性背后的分子基础仍是一个悬而未决的问题。在本研究中，一种新的提取和纯化方法成功应用于从卡介苗中分离甘露糖基化脂阿拉伯甘露聚糖（ManLAMs，具有甘露糖基延伸的脂阿拉伯甘露聚糖），从而获得了两种类型的ManLAMs，即壁膜型和细胞型。在结构上，发现它们的甘露寡糖帽百分比不同，分别为76%和48%，而且，由于一种新的分析方法，它们的磷脂酰 - 肌醇锚定脂质部分的结构也不同。分枝杆菌属中的一种新型脂肪酸，即12 - O -（甲氧基丙酰基）- 12 - 羟基硬脂酸，是壁膜型ManLAMs甘油残基C - 1位唯一的酯化脂肪酸，而细胞型ManLAMs的磷脂酰单元由于棕榈酸和结核硬脂酸的组合而表现出很大的异质性。最后，发现壁膜型和细胞型ManLAMs对人树突状细胞分泌白细胞介素 - 8和肿瘤坏死因子 - α有不同影响。我们发现壁膜型而非细胞型ManLAMs能够刺激树突状细胞分泌肿瘤坏死因子 - α。从这些研究中我们提出，1 - [12 - O -（甲氧基丙酰基）- 12 - 羟基硬脂酰基] - sn - 甘油部分是ManLAMs的主要细胞因子调节成分。在恶劣环境中可能发生的ManLAM脂质部分的修饰，似乎有可能通过改变细胞因子刺激来调节巨噬细胞内分枝杆菌的存活。
