Profiles of structural heterogeneity in native lipooligosaccharides of Neisseria and cytokine induction
Profiles of structural heterogeneity in native lipooligosaccharides of Neisseria and cytokine induction
复制标题
DOI：
10.1194/jlr.m800184-jlr200
复制
发表时间：
2009-03-01
影响因子：
6.5
通讯作者：
Jarvis, Gary A.
中科院分区：
文献类型：
--
作者：
John, Constance M.;Liu, Mingfeng;Jarvis, Gary A.
奈瑟氏菌属的脂寡糖（LOS）的磷酸化和酰化的细微差异被认为深刻地影响生物体的毒力和宿主的先天免疫应答，例如通过Toll样受体4（TLR 4）和髓样细胞上表达的触发受体（TREM）的信号传导。采用MALDI飞行时间（TOF）质谱法表征淋病奈瑟菌和奈瑟菌天然LOS的异质性。脑膜炎使用先前报道的用于大肠杆菌脂多糖（LPS）的样品制备方法，所述样品制备方法采用将未处理的LOS沉积在由2，4，6-三羟基苯乙酮和硝化纤维素组成的薄膜的薄层上。观察到对应于分子离子和碎片离子的突出峰，所述碎片离子主要由3-脱氧-D-甘露-辛-2-酮糖酸（Kdo）和脂质A（LA）之间的裂解形成。这些数据的分析和光谱的相应的O-脱酰或氟化氢处理的LOS的比较，使检测的新物种，显然不同的表达高达三个磷酸盐与一个或多个磷酸乙醇胺（PEA）组的LA。我们发现酰化和磷酸化的异质性与THP-1单核细胞中促炎细胞因子的诱导相关。这种方法使我们能够快速分析具有生物学意义的天然LOS结构变体的组成部分。约翰角M.，M. Liu和G. A.贾维斯奈瑟氏菌天然脂寡糖的结构异质性和细胞因子诱导。J. Lipid Res. 2009. 50：424-438。
Fine differences in the phosphorylation and acylation of lipooligosaccharide (LOS) from Neisseria species are thought to profoundly influence the virulence of the organisms and the innate immune responses of the host, such as signaling through toll-like receptor 4 (TLR4) and triggering receptor expressed on myeloid cells (TREM). MALDI time-of-flight (TOF) mass spectrometry was used to characterize heterogeneity in the native LOS from Neisseria gonorrheae and N. meningitidis. A sample preparation methodology previously reported for Escherichia coli lipopolysaccharide (LPS) employing deposition of untreated LOS on a thin layer of a film composed of 2,4,6-trihydroxyacetophenone and nitrocellulose was used. Prominent peaks were observed corresponding to molecular ions and to fragment ions primarily formed by cleavage between the 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) and the lipid A (LA). Analyses of these data and comparison with spectra of the corresponding O-deacylated or hydrogen fluoride-treated LOS enabled the detection of novel species that apparently differed by the expression of up to three phosphates with one or more phosphoethanolamine (PEA) groups on the LA. We found that the heterogeneity profile of acylation and phosphorylation correlates with the induction of proinflammatory cytokines in THP-1 monocytic cells. This methodology enabled us to rapidly profile components of structural variants of native LOS that are of importance biologically.-John, C. M., M. Liu, and G. A. Jarvis. Profiles of structural heterogeneity in native lipooligosaccharides of Neisseria and cytokine induction. J. Lipid Res. 2009. 50: 424-438.