Physicochemical characterization and biological activity of a glycoglycerolipid from Mycoplasma fermentans
Physicochemical characterization and biological activity of a glycoglycerolipid from Mycoplasma fermentans
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DOI：
10.1046/j.1432-1033.2003.03719.x
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发表时间：
2003-08-01
期刊：
影响因子：
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通讯作者：
Seydel, U
中科院分区：
文献类型：
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作者：
Brandenburg, K;Wagner, F;Seydel, U
我们报告了发酵支原体 MfGl-II 的糖甘油脂与其生物活性相关的综合理化特性，并将其与来自深层粗糙突变体明尼苏达沙门氏菌菌株 R595 的磷脂酰胆碱 (PC) 和细菌糖脂、脂多糖 (LPS) 的各自行为进行了比较。 MfGl-II 和 LPS 在 T (c) = 30°C 时烃链的 βα 凝胶到液晶相变行为表现出两种糖脂之间的高度相似性。两种糖脂均观察到脂多糖结合蛋白（LBP）介导的掺入带负电荷的脂质体。超分子聚集体结构的测定证实了 MfGl-II 混合单层/立方结构的存在，类似于 LPS 脂质 A 部分观察到的结构。生物学数据清楚地表明，MfG1-II能够在人单核细胞中诱导细胞因子，例如肿瘤坏死因子-α(TNF-α)，尽管程度显着低于LPS。相反，在鲎变形细胞裂解物测试中，MfGl-II完全失活，并且在CHO报告细胞系中，与对照脂肽和LPS相比，它没有表明与Toll样受体TLR-2和-4有任何反应性。这些数据证实了我们的内毒性构象概念对非脂质 A 结构的适用性：具有非层状立方聚集结构的两亲性分子，对应于单分子的圆锥形构象和主链中足够高的负电荷密度。
We report a comprehensive physicochemical characterization of a glycoglycerolipid from Mycoplasma fermentans , MfGl-II, in relation to its bioactivity and compared this with the respective behaviors of phosphatidylcholine (PC) and a bacterial glycolipid, lipopolysaccharide (LPS) from deep rough mutant Salmonella minnesota strain R595. The betaalpha gel-to-liquid crystalline phase transition behavior of the hydrocarbon chains with T (c) = 30 degreesC for MfGl-II as well as for LPS exhibits high similarity between the two glycolipids. A lipopolysaccharide-binding protein (LBP)-mediated incorporation into negatively charged liposomes is observed for both glycolipids. The determination of the supramolecular aggregate structure confirms the existence of a mixed unilamellar/cubic structure for MfGl-II, similar to that observed for the lipid A moiety of LPS. The biological data clearly show that MfGl-II is able to induce cytokines such as tumor necrosis factor-alpha (TNF-alpha) in human mononuclear cells, although to a significantly lower degree than LPS. In contrast, in the Limulus amebocyte lysate test, MfGl-II is completely inactive, and in the CHO reporter cell line it does not indicate any reactivity with the Toll-like receptors TLR-2 and -4, in contrast to control lipopeptides and LPS. These data confirm the applicability of our conformational concept of endotoxicity to nonlipid A structures: an amphiphilic molecule with a nonlamellar cubic aggregate structure corresponding to a conical conformation of the single molecules and a sufficiently high negative charge density in the backbone.