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Cytoadherence characteristics to endothelial receptors ICAM-1 and CD36 of Plasmodium falciparum populations from severe and uncomplicated malaria cases

机译:严重和不复杂疟疾病例恶性疟原虫人群对内皮受体ICAM-1和CD36的细胞粘附特性

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The adhesion of infected red blood cells (IRBCs) to the cell lining of microvasculature is thought to play a central role in the pathogenesis of severe malaria. Individual IRBC can bind to more than one host receptor and parasites with multiple binding phenotypes may cause severe disease more frequently. However, as most clinical isolates are multiclonal, previous studies were hampered by the difficulty to distinguish whether a multiadherent phenotype was due to one or more parasite population(s). We have developed a tool, based on cytoadhesion assay and GeneScan genotyping technology, which enabled us to assess on fresh isolates the capacity of adherence of individual P. falciparum genotypes to human receptors expressed on CHO transfected cells. The cytoadhesion to ICAM-1 and CD36 of IRBCs from uncomplicated and severe malaria attacks was evaluated using this methodology. In this preliminary series conducted in non immune travelers, IRBCs from severe malaria appeared to adhere more frequently and/or strongly to ICAM-1 and CD36 in comparison with uncomplicated cases. In addition, a majority genotype able to strongly adhere to CD36 was found more frequently in isolates from severe malaria cases. Further investigations are needed to confirm the clinical relevance of these data.
机译:人们认为,感染的红细胞(IRBC)与微血管系统细胞壁的粘附在严重疟疾的发病机理中起着核心作用。单个IRBC可以与一种以上的宿主受体结合,具有多种结合表型的寄生虫可能更频繁地导致严重疾病。然而,由于大多数临床分离株是多克隆的,以前的研究因难以区分多粘附表型是否是由于一个或多个寄生虫种群而受到阻碍。我们已经开发出一种基于细胞粘附测定和GeneScan基因分型技术的工具,该工具使我们能够评估新鲜的分离株恶性疟原虫基因型对CHO转染细胞上表达的人类受体的粘附能力。使用这种方法评估了来自简单和严重疟疾发作的IRBC对ICAM-1和CD36的细胞粘附性。在非免疫旅行者中进行的这一初步系列研究中,与简单病例相比,来自严重疟疾的IRBC似乎更频繁和/或更牢固地粘附于ICAM-1和CD36。另外,在严重疟疾病例的分离株中,能够更牢固地粘附于CD36的多数基因型更为常见。需要进一步的研究以确认这些数据的临床相关性。

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