Chaisavaneeyakorn Sujittra, Kongtawelert Prachya, Angkasekwinai Pornpimon, McGready Rose, Nosten François, Chaiyaroj Sansanee C
Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Am J Trop Med Hyg. 2004 Feb;70(2):149-57.
Chondroitin sulfate A (CSA) is an important receptor for Plasmodium falciparum-infected erythrocytes in the placenta. To study the molecular interaction between parasitized erythrocytes (PE) to CSA, we performed in vitro cytoadherence inhibition assays of PE infected with wild and laboratory isolates of P. falciparum to CSA using various glycosaminoglycans (GAGs). Marked decrease in PE adhesion to immobilized CSA and CSA-expressed cells was achieved with soluble chondroitin sulfate D (CSD) and chondroitin sulfate E (CSE) at low concentrations. The effect was dose dependent with the degree of inhibition exceeded that of soluble CSA in certain clinical isolates. The results suggested the influence of oversulfation of CS variant chains on PE adherence to CSA. Interestingly, PE of the tested wild isolates could adhere to immobilized CSD and CSE at different levels while PE of CSA-selected laboratory lines could not. Partial inhibitory activity was observed when chondroitin sulfate C (CSC), chondroitin sulfate B (CSB), and polyolpolysulfate were used even at high concentrations. Keratan sulfate, colominic acid, and Suramine were unable to inhibit PE adherence. Taken together, the results confirm that the 4-sulfate amino sugar moiety, as well as the basic disaccharide structure of N-acetylgalactosamine linked to glucuronic acid, may influence the degree of this molecular interaction. However, other sulfation patterns that could influence the interaction could not be overlooked, as in the case of CSD which contains 2-O-sulfation at glucuronic acid. Studies using pentosan polysulfate, an oversulfated molecule with a xylan backbone, as an inhibitor also showed a reduction of PE adherence of most isolates tested. Thus, only the sulfate content and pattern of this molecule could affect the adhesive interactions. In addition, difference in capacity of low molecular weight heparins to inhibit CSA-mediated PE cytoadherence of clinical isolates was also observed, thereby providing evidence on the heterogeneity in cytoadherence characteristics of maternal parasite isolates as well as their therapeutic potentials.
硫酸软骨素A(CSA)是胎盘内恶性疟原虫感染红细胞的重要受体。为了研究被寄生红细胞(PE)与CSA之间的分子相互作用,我们使用各种糖胺聚糖(GAG)对感染了恶性疟原虫野生株和实验室分离株的PE进行了体外细胞黏附抑制试验。低浓度的可溶性硫酸软骨素D(CSD)和硫酸软骨素E(CSE)可使PE与固定化CSA及表达CSA的细胞的黏附显著减少。该效应呈剂量依赖性,在某些临床分离株中,抑制程度超过了可溶性CSA。结果表明CS变异链的过度硫酸化对PE与CSA的黏附产生影响。有趣的是,所测试的野生分离株的PE能以不同水平黏附于固定化的CSD和CSE,而CSA选择的实验室株的PE则不能。即使在高浓度下使用硫酸软骨素C(CSC)、硫酸软骨素B(CSB)和聚醇硫酸酯,也仅观察到部分抑制活性。硫酸角质素、大肠杆菌多糖酸和苏拉明不能抑制PE黏附。综上所述,结果证实4-硫酸氨基糖部分以及与葡萄糖醛酸相连的N-乙酰半乳糖胺的基本二糖结构可能影响这种分子相互作用的程度。然而,其他可能影响相互作用的硫酸化模式也不能被忽视,如含有葡萄糖醛酸2-O-硫酸化的CSD的情况。使用具有木聚糖主链的过度硫酸化分子戊聚糖多硫酸酯作为抑制剂的研究也表明,所测试的大多数分离株的PE黏附减少。因此,只有该分子的硫酸含量和模式会影响黏附相互作用。此外,还观察到低分子量肝素抑制临床分离株CSA介导的PE细胞黏附的能力存在差异,从而为母体寄生虫分离株细胞黏附特征的异质性及其治疗潜力提供了证据。