Cytoadhesion of Plasmodium falciparum-infected erythrocytes to chondroitin-4-sulfate is cooperative and shear enhanced.
Cytoadhesion of Plasmodium falciparum-infected erythrocytes to chondroitin-4-sulfate is cooperative and shear enhanced.
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DOI：
10.1182/blood-2014-03-561019
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发表时间：
2015-01
期刊：
影响因子：
20.3
通讯作者：
Harden Rieger;H. Yoshikawa;Katharina A. Quadt;M. Nielsen;Cecilia P. Sanchez;A. Salanti;Motomu Tanaka;M. Lanzer
中科院分区：
文献类型：
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作者：
Harden Rieger;H. Yoshikawa;Katharina A. Quadt;M. Nielsen;Cecilia P. Sanchez;A. Salanti;Motomu Tanaka;M. Lanzer
妊娠期间感染人类疟疾寄生虫恶性疟原虫可导致母亲和婴儿的严重并发症，这是由胎盘绒毛间隙中的寄生红细胞的细胞粘附引起的。细胞粘附是由寄生虫编码的粘附素VAR 2CSA与胎盘蛋白多糖上的4-硫酸软骨素（CSA）的特异性相互作用赋予的。CSA在微血管系统中的其他地方不提供VAR 2CSA介导的寄生红细胞的细胞粘附。为了解决胎盘特异性结合向性，我们研究了受体/配体排列对细胞粘附的影响，使用具有不同CSA间距的人工膜。我们发现细胞粘附强烈依赖于CSA距离，在所有流体动力学条件下，CSA距离为9 ± 1 nm时出现半最大粘附。此外，结合CSA是合作和剪切应力诱导。这些发现表明CSA密度以及VAR 2CSA中的变构效应有助于区分不同的CSA环境。
Infections with the human malaria parasite Plasmodium falciparum during pregnancy can lead to severe complications for both mother and child, resulting from the cytoadhesion of parasitized erythrocytes in the intervillous space of the placenta. Cytoadherence is conferred by the specific interaction of the parasite-encoded adhesin VAR2CSA with chondroitin-4-sulfate (CSA) present on placental proteoglycans. CSA presented elsewhere in the microvasculature does not afford VAR2CSA-mediated cytoadhesion of parasitized erythrocytes. To address the placenta-specific binding tropism, we investigated the effect of the receptor/ligand arrangement on cytoadhesion, using artificial membranes with different CSA spacing intervals. We found that cytoadhesion is strongly dependent on the CSA distance, with half-maximal adhesion occurring at a CSA distance of 9 ± 1 nm at all hydrodynamic conditions. Moreover, binding to CSA was cooperative and shear stress induced. These findings suggest that the CSA density, together with allosteric effects in VAR2CSA, aid in discriminating between different CSA milieus.