Adhesion of Plasmodium falciparum infected erythrocytes in ex vivo perfused placental tissue: a novel model of placental malaria.
Adhesion of Plasmodium falciparum infected erythrocytes in ex vivo perfused placental tissue: a novel model of placental malaria.
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DOI：
10.1186/s12936-016-1342-2
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发表时间：
2016-05-26
期刊：
影响因子：
3
通讯作者：
Nielsen MA
中科院分区：
文献类型：
--
作者：
Pehrson C;Mathiesen L;Heno KK;Salanti A;Resende M;Dzikowski R;Damm P;Hansson SR;King CL;Schneider H;Wang CW;Lavstsen T;Theander TG;Knudsen LE;Nielsen MA
当恶性疟原虫感染的红细胞在胎盘中隔离时，就会发生胎盘性疟疾。胎盘寄生虫分离株通过在感染的红细胞表面表达VAR2CSA与硫酸软骨素A(CSA)结合，但也可以通过VAR2CSA介导的其他机制隔离，如与免疫球蛋白结合。此外，其他寄生虫抗原也与胎盘性疟疾有关。这些发现对胎盘型疟疾疫苗的设计具有重要意义。这项研究的目的是适应和描述一种与生物相关的寄生虫在完整胎盘组织中黏附的模型。对体外胎盘灌流模型进行了改进，以研究感染红细胞与环孢素A、内皮蛋白C受体(EPCR)或恶性疟原虫红细胞膜蛋白1表达缺失的转基因寄生虫的粘附性。感染的表达VAR2CSA的红细胞聚集在灌流的胎盘组织中，而EPCR结合和转基因寄生虫则没有。可溶性CsA和抗VAR2CsA抗体可抑制感染红细胞的结合。体外模型为研究胎盘疟疾受体-配体相互作用和抗体介导的结合抑制提供了一种新的方法。本文的在线版本(doi：10.1186/s12936-016-1342-2)包含补充材料，授权用户可以使用。
Placental malaria occurs when Plasmodium falciparum infected erythrocytes sequester in the placenta. Placental parasite isolates bind to chondroitin sulphate A (CSA) by expression of VAR2CSA on the surface of infected erythrocytes, but may sequester by other VAR2CSA mediated mechanisms, such as binding to immunoglobulins. Furthermore, other parasite antigens have been associated with placental malaria. These findings have important implications for placental malaria vaccine design. The objective of this study was to adapt and describe a biologically relevant model of parasite adhesion in intact placental tissue. The ex vivo placental perfusion model was modified to study adhesion of infected erythrocytes binding to CSA, endothelial protein C receptor (EPCR) or a transgenic parasite where P. falciparum erythrocyte membrane protein 1 expression had been shut down. Infected erythrocytes expressing VAR2CSA accumulated in perfused placental tissue whereas the EPCR binding and the transgenic parasite did not. Soluble CSA and antibodies specific against VAR2CSA inhibited binding of infected erythrocytes. The ex vivo model provides a novel way of studying receptor-ligand interactions and antibody mediated inhibition of binding in placental malaria. The online version of this article (doi:10.1186/s12936-016-1342-2) contains supplementary material, which is available to authorized users.