Chondroitin sulphate A (CSA)-binding of single recombinant Duffy-binding-like domains is not restricted to Plasmodium falciparum Erythrocyte Membrane Protein 1 expressed by CSA-binding parasites
Chondroitin sulphate A (CSA)-binding of single recombinant Duffy-binding-like domains is not restricted to Plasmodium falciparum Erythrocyte Membrane Protein 1 expressed by CSA-binding parasites
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DOI：
10.1016/j.ijpara.2009.02.022
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发表时间：
2009-09-01
影响因子：
4
通讯作者：
Dahlback, Madeleine
中科院分区：
文献类型：
--
作者：
Resende, Mafalda;Ditlev, Sisse B.;Dahlback, Madeleine
生活在恶性疟原虫高传播地区的个人随着时间的推移获得对疟疾的免疫力，成年人感染严重疾病的风险明显降低。然而，孕妇是一个重要的例外。妊娠相关疟疾是导致母亲和后代发病的主要原因，如严重的母体贫血和低出生体重，其特征是胎盘中寄生虫感染的红细胞（IE）的选择性积累。一种名为VAR2CSA的恶性疟原虫蛋白，属于大型恶性疟原虫红细胞膜蛋白1（PfEMP 1）家族，使IE能够结合胎盘中的硫酸软骨素A（CSA）。敲除研究已经证明了VAR2CSA介导IE与CSA结合的唯一能力，并且已经显示VAR2CSA的六个Duffy结合样（DBL）结构域中的四个具有体外结合CSA的能力。在这项研究中，我们证实了CSA结合这些DBL结构域，然而，一些非VAR2CSA来源的DBL结构域的分析表明，CSA结合并不完全限于VAR2CSA DBL结构域。此外，我们表明，VAR2CSA DBL结构域以及其他DBL结构域也结合硫酸乙酰肝素。这些数据解释了许多出版物描述的CSA结合域来自PfEMP 1抗原不参与胎盘粘连。这些数据表明，单一结构域结合CSA的能力并不能预测整个PfEMP 1的功能能力，并对天然VAR2CSA的CSA结合结构域是否已被正确鉴定提出了疑问。(C)2009年澳大利亚寄生虫学会由爱思唯尔有限公司出版。保留所有权利。
Individuals living in areas with high Plasmodium falciparum transmission acquire immunity to malaria over time and adults have a markedly reduced risk of contracting severe disease. However, pregnant women constitute an important exception. Pregnancy-associated malaria is a major cause of mother and offspring morbidity, such as severe maternal anaemia and low birth-weight, and is characterised by selective accumulation of parasite-infected erythrocytes (IE) in the placenta. A P. falciparum protein named VAR2CSA, which belongs to the large P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) family, enables the IE to bind chondroitin sulphate A (CSA) in the placenta. Knock-out studies have demonstrated the exclusive capacity of VAR2CSA to mediate IE binding to CSA, and it has been shown that four of the six Duffy-binding-like (DBL) domains of VAR2CSA have the ability to bind CSA in vitro. In this study, we confirm the CSA-binding of these DBL domains, however, the analysis of a number of DBL domains of a non-VAR2CSA origin shows that CSA-binding is not exclusively restricted to VAR2CSA DBL domains. Furthermore, we show that the VAR2CSA DBL domains as well as other DBL domains also bind heparan sulphate. These data explain a number of publications describing CSA-binding domains derived from PfEMP1 antigens not involved in placental adhesion. The data suggest that the ability of single domains to bind CSA does not predict the functional capacity of the whole PfEMP1 and raises doubt whether the CSA-binding domains of native VAR2CSA have been correctly identified. (C) 2009 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.