Plasmodium falciparum expressing domain cassette 5 type PfEMP1 (DC5-PfEMP1) bind PECAM1.
Plasmodium falciparum expressing domain cassette 5 type PfEMP1 (DC5-PfEMP1) bind PECAM1.
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DOI：
10.1371/journal.pone.0069117
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lavstsen T
中科院分区：
文献类型：
--
作者：
Berger SS;Turner L;Wang CW;Petersen JE;Kraft M;Lusingu JP;Mmbando B;Marquard AM;Bengtsson DB;Hviid L;Nielsen MA;Theander TG;Lavstsen T
恶性疟原虫红细胞膜蛋白1（PfEMP 1）家族成员在疟疾感染的红细胞表面上表达，介导寄生虫与血管衬里上的不同受体的结合。这个过程驱动病理学，严重的儿童疟疾与PfEMP 1分子的特定子集的表达有关。PfEMP 1基于上游序列和称为结构域盒（DC）的半保守PfEMP 1结构域组合物的存在被分为亚型。早期的研究表明，含DC 5的PfEMP 1（DC 5-PfEMP 1）在患有严重疟疾的儿童中比在患有无并发症疟疾的儿童中更有可能表达，但这些PfEMP 1亚型仅在相对较小比例的患有严重疾病的儿童中占主导地位。在这项研究中，我们已经表征了DC 5的基因组序列特征，并表明两种基因不同的寄生虫系表达DC 5-PfEMP 1结合PECAM 1，抗DC 5特异性抗体抑制DC 5-PfEMP 1表达寄生虫与转化的人骨髓内皮细胞（TrHBMEC）的结合。我们还表明，针对DC 5的四个结构域中的每一个的抗体与受感染的红细胞表面上表达的天然PfEMP 1反应，并且其中一些抗体在两个含DC 5的PfEMP 1分子之间具有交叉反应性。最后，我们证实，抗DC 5抗体是由生活在疟疾流行地区的个人在生命早期获得的，这些抗体水平高的个人不太可能发展为发热性疟疾发作，抗体水平与血红蛋白水平呈正相关。
Members of the Plasmodium falciparum Erythrocyte Membrane protein 1 (PfEMP1) family expressed on the surface of malaria-infected erythrocytes mediate binding of the parasite to different receptors on the vascular lining. This process drives pathologies, and severe childhood malaria has been associated with the expression of particular subsets of PfEMP1 molecules. PfEMP1 are grouped into subtypes based on upstream sequences and the presence of semi-conserved PfEMP1 domain compositions named domain cassettes (DCs). Earlier studies have indicated that DC5-containing PfEMP1 (DC5-PfEMP1) are more likely to be expressed in children with severe malaria disease than in children with uncomplicated malaria, but these PfEMP1 subtypes only dominate in a relatively small proportion of the children with severe disease. In this study, we have characterised the genomic sequence characteristic for DC5, and show that two genetically different parasite lines expressing DC5-PfEMP1 bind PECAM1, and that anti-DC5-specific antibodies inhibit binding of DC5-PfEMP1-expressing parasites to transformed human bone marrow endothelial cells (TrHBMEC). We also show that antibodies against each of the four domains characteristic for DC5 react with native PfEMP1 expressed on the surface of infected erythrocytes, and that some of these antibodies are cross-reactive between the two DC5-containing PfEMP1 molecules tested. Finally, we confirm that anti-DC5 antibodies are acquired early in life by individuals living in malaria endemic areas, that individuals having high levels of these antibodies are less likely to develop febrile malaria episodes and that the antibody levels correlate positively with hemoglobin levels.
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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
4.4
作者：
Cham, Gerald K. K.;Turner, Louise;Theander, Thor G.
通讯作者：
Theander, Thor G.
DOI：
10.1074/jbc.m112.416347
发表时间：
2013-02-22
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Brown A;Turner L;Christoffersen S;Andrews KA;Szestak T;Zhao Y;Larsen S;Craig AG;Higgins MK
通讯作者：
Higgins MK
影响因子：
64.5
作者：
BARUCH, DI;PASLOSKE, BL;HOWARD, RJ
通讯作者：
HOWARD, RJ
影响因子：
6.4
作者：
Bigey, Pascal;Gnidehou, Sedami;Ndam, Nicaise Tuikue
通讯作者：
Ndam, Nicaise Tuikue