Synthetic lipoteichoic acid from Staphylococcus aureus is a potent stimulus of cytokine release.
Synthetic lipoteichoic acid from Staphylococcus aureus is a potent stimulus of cytokine release.
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金黄色葡萄球菌中的合成脂肪酸是细胞因子释放的有效刺激。
DOI：
10.1084/jem.20020322
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发表时间：
2002-06-17
影响因子：
15.3
通讯作者：
Hartung, Thomas
中科院分区：
文献类型：
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作者：
Morath, Siegfried;Stadelmaier, Andreas;Geyer, Armin;Schmidt, Richard R;Hartung, Thomas
最近，我们纯化脂磷壁酸（LTA）从金黄色葡萄球菌的纯度超过99%的一种新的制备方法，并推导出其结构与第一个完整的LTA的核磁共振（NMR）。与革兰氏阴性脂多糖相反，这种LTA需要toll样受体（TLR）-2而不是TLR-4来诱导单核细胞和巨噬细胞中的细胞因子。阐明S.金黄色葡萄球菌中，通过天然LTA的酸性水解或化学合成（龙胆糖基-sn-二肉豆蔻酰甘油）制备脂质锚定物。接下来，合成了具有六个甘油磷酸单元的完整LTA分子，其携带四个丙氨酸加一个N-乙酰基-葡糖胺取代基，其显示出与天然LTA相同的激活单核细胞的效力。然而，细胞因子诱导需要高100- 1，000倍浓度的脂质锚。值得注意的是，用l-丙氨酸替代d-丙氨酸减弱了指示立体选择性识别的效果。通过核磁共振和基质辅助激光解吸电离质谱对合成的具有生物活性的LTA进行了结构鉴定。我们的结论是，脂质锚，其脂肪酸，代表LTA的免疫刺激活性的一个组成部分，但需要额外的结构组件上的聚甘油磷酸骨架。
We recently purified lipoteichoic acid (LTA) from Staphylococcus aureus to more than 99% purity by a novel preparation method and deduced its structure with the first nuclear magnetic resonance (NMR) of a complete LTA. In contrast to Gram-negative lipopolysaccharides, this LTA requires the toll-like receptor (TLR)-2 and not TLR-4 for cytokine induction in monocytes and macrophages. To elucidate the structure–function relationships for LTA from S. aureus, the lipid anchor was prepared by either acidic hydrolysis of native LTA or chemical synthesis (gentiobiosyl-sn-dimyristoylglycerol). Next, a complete LTA molecule with six glycerophosphate units carrying four alanine plus one N-acetyl-glucosamine substituent was synthesized, which displayed the same potency to activate monocytes as native LTA. However, 100–1,000 times higher concentrations of the lipid anchor were required for cytokine induction. It is worthy to note that replacing d-alanine with l-alanine blunted the effect indicating stereoselective recognition. The structure identification of this synthesized and biologically active LTA was proven by NMR and matrix-assisted laser desorption-ionization mass spectrometry. We concluded that the lipid anchor, with its fatty acids, represents an integral part of the immunostimulatory activity of LTA, but requires additional structural components on the polyglycerophosphate backbone.