Beeson J G, Chai W, Rogerson S J, Lawson A M, Brown G V
Division of Infection and Immunity, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Infect Immun. 1998 Jul;66(7):3397-402. doi: 10.1128/IAI.66.7.3397-3402.1998.
Adherence of parasite-infected erythrocytes (IEs) to the microvascular endothelium of various organs, a process known as sequestration, is a feature of Plasmodium falciparum malaria. 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.
被寄生虫感染的红细胞（IEs）黏附于各器官的微血管内皮，这一过程称为隔离，是恶性疟原虫疟疾的一个特征。该事件由IEs表面表达的寄生虫蛋白与宿主分子之间的特异性黏附相互作用介导。恶性疟原虫IEs可与纯化的硫酸软骨素A（CS-A）结合，通过CS-A侧链与蛋白聚糖血栓调节蛋白结合，并与脑和肺内皮细胞及胎盘合体滋养层细胞表面的CS-A结合。为了确定对结合重要的CS-A的结构特征，在受控的软骨素裂解酶消化后，从CS-A和CS-C中分离出大小从2到20个单糖单元不等的寡糖片段，并用作IEs与固定化配体结合的竞争性抑制剂。对CS-A结合的抑制高度依赖于分子大小：CS-A十四糖部分是能够几乎完全抑制结合的最小长度。这种作用是剂量依赖性的，与母体多糖相似，而CS-C寡糖未发现相同程度的抑制作用。对IEs与其他配体（如CD36和细胞间黏附分子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抑制与血栓调节蛋白结合所必需的。通过电喷雾质谱和高效液相色谱对寡糖部分和多糖进行分析表明，CS-A和CS-C寡糖活性的差异可归因于硫酸盐含量和硫酸化模式的差异，且艾杜糖醛酸不参与IEs结合。
