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首页> 外文期刊>Infection and immunity >Inhibition of Binding of Malaria-Infected Erythrocytes by a Tetradecasaccharide Fraction from Chondroitin Sulfate A
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Inhibition of Binding of Malaria-Infected Erythrocytes by a Tetradecasaccharide Fraction from Chondroitin Sulfate A

机译:硫酸软骨素A的四糖部分抑制疟疾感染的红细胞的结合。

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Adherence of parasite-infected erythrocytes (IEs) to the microvascular endothelium of various organs, a process known as sequestration, is a feature of Plasmodium falciparummalaria. This event is mediated by specific adhesive interactions between parasite proteins, expressed on the surface of IEs, and host molecules. P. falciparum IEs can bind to purified chondroitin sulfate A (CS-A), to the proteoglycan thrombomodulin through CS-A side chains, and to CS-A present on the surface of brain and lung endothelial cells and placental syncytiotrophoblasts. In order to identify structural characteristics of CS-A important for binding, oligosaccharide fragments ranging in size from 2 to 20 monosaccharide units were isolated from CS-A and CS-C, following controlled chondroitin lyase digestion, and used as competitive inhibitors of IE binding to immobilized ligands. Inhibition of binding to CS-A was highly dependent on molecular size: a CS-A tetradecasaccharide fraction was the minimum length able to almost completely inhibit binding. The effect was dose dependent and similar to that of the parent polysaccharide, and the same degree of inhibition was not found with the CS-C oligosaccharides. There was no effect on binding of IEs to other ligands, e.g., CD36 and intercellular adhesion molecule 1. Hexadeca- and octadecasaccharide fractions of CS-A were required for maximum inhibition of binding to thrombomodulin. Analyses of oligosaccharide fractions and polysaccharides by electrospray mass spectrometry and high-performance liquid chromatography suggest that the differences between the activities of CS-A and CS-C oligosaccharides can be attributed to differences in sulfate content and sulfation pattern and that iduronic acid is not involved in IE binding.
机译:疟原虫是疟原虫的特征之一,寄生虫感染的红细胞(IEs)附着在各个器官的微血管内皮上。此事件是由在IE表面上表达的寄生虫蛋白与宿主分子之间的特异性粘附相互作用介导的。 P。恶性疟原虫可与纯化的硫酸软骨素A(CS-A)结合,并通过CS-A侧链与蛋白聚糖血栓调节蛋白结合,并与存在于脑和肺内皮细胞和胎盘合体滋养层细胞表面的CS-A结合。为了鉴定对结合重要的CS-A的结构特征,在控制软骨素裂解酶消化后,从CS-A和CS-C中分离了大小为2至20个单糖单元的寡糖片段,并用作IE结合的竞争性抑制剂。固定化的配体。抑制与CS-A的结合高度依赖于分子大小:CS-A十四碳糖部分是能够几乎完全抑制结合的最小长度。该作用是剂量依赖性的并且类似于母体多糖的作用,并且对于CS-C寡糖未发现相同程度的抑制。对IE与其他配体例如CD36和细胞间粘附分子1的结合没有影响。CS-A的十六糖和十八糖部分是最大程度地抑制与血栓调节蛋白结合所需的。通过电喷雾质谱和高效液相色谱法分析寡糖馏分和多糖,表明CS-A和CS-C寡糖活性之间的差异可归因于硫酸盐含量和硫酸化模式的差异,而不涉及艾杜糖酸在IE绑定中。

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