The charge of endotoxin molecules influences their conformation and IL-6-inducing capacity.
The charge of endotoxin molecules influences their conformation and IL-6-inducing capacity.
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内毒素分子的电荷影响其构象和 IL-6 诱导能力。
DOI：
10.4049/jimmunol.161.10.5464
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发表时间：
1998
影响因子：
4.4
通讯作者：
U. Seydel
中科院分区：
文献类型：
--
作者：
A. Schromm;K. Brandenburg;H. Loppnow;U. Zähringer;E. Rietschel;S. Carroll;M. Koch;S. Kusumoto;U. Seydel
内毒素（LPS）激活细胞是宿主对革兰氏阴性菌感染的早期反应之一。脂多糖分子的脂质A部分代表内毒原理；然而，对生物活性表达的具体要求尚不完全清楚。我们以前发现，特定的分子构象（内毒构象）是脂质a具有生物活性的先决条件。在这项研究中，我们研究了天然和化学修饰的LPS与脂质A的分子电荷和构象的相互依赖性，以及在人LPS结合蛋白介导下其转运和嵌入磷脂膜，以及刺激全血或PBMCs后IL-6的产生。我们发现负电荷的数量、性质和位置强烈地调节内毒素的分子构象。此外，脂多糖结合蛋白介导的脂多糖进入磷脂膜的运输依赖于净负电荷的存在，然而电荷只是运输和嵌入的必要条件，而不是充分条件。生物活性主要由分子的构象决定，只有锥形分子具有高度的生物活性，而圆柱形分子基本上没有活性。我们可以证明，脂质A组分的净负电荷及其在亲水头基中的分布强烈影响分子构象，因此也影响生物活性。
The activation of cells by endotoxin (LPS) is one of the early host responses to infections with Gram-negative bacteria. The lipid A part of LPS molecules is known to represent the endotoxic principle; however, the specific requirements for the expression of biologic activity are still not fully understood. We previously found that a specific molecular conformation (endotoxic conformation) is a prerequisite for lipid A to be biologically active. In this study, we have investigated the interdependence of molecular charge and conformation of natural and chemically modified LPS and lipid A and its transport and intercalation into phospholipid membranes mediated by human LPS-binding protein, as well as IL-6 production after stimulation of whole blood or PBMCs. We found that the number, nature, and location of negative charges strongly modulate the molecular conformation of endotoxin. In addition, the LPS-binding protein-mediated transport of LPS into phospholipid membranes depends on the presence of net negative charge, yet charge is only a necessary, but not a sufficient, prerequisite for transport and intercalation. The biologic activity is determined mainly by the molecular conformation: only conical molecules are highly biologically active, whereas cylindrical ones are largely inactive. We could demonstrate that the net negative charge of the lipid A component and its distribution within the hydrophilic headgroup strongly influence the molecular conformation and, therefore, also the biologic activity.
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影响因子：
2.8
作者：
TOBIAS, PS;ULEVITCH, RJ
通讯作者：
ULEVITCH, RJ
影响因子：
56.9
作者：
WRIGHT, SD;RAMOS, RA;MATHISON, JC
通讯作者：
MATHISON, JC
DOI：
10.1073/pnas.90.7.2744
发表时间：
1993-04-01
影响因子：
11.1
作者：
PUGIN, J;SCHURERMALY, CC;TOBIAS, PS
通讯作者：
TOBIAS, PS
脂多糖结合蛋白和可溶性 CD14 将脂多糖转移到磷脂双层：优先与特定类别的脂质相互作用。
DOI：
--
发表时间：
1997
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Wurfel,MM;Wright,SD
通讯作者：
Wright,SD
激活 B 淋巴细胞的脂多糖单元的理化特性。
DOI：
--
发表时间：
1990
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Takayama,K;Din,ZZ;Mukerjee,P;Cooke,PH;Kirkland,TN
通讯作者：
Kirkland,TN