Plasmodium falciparum:: Molecular background to strain-specific rosette disruption by glycosaminoglycans and sulfated glycoconjugates

Plasmodium falciparum:: Molecular background to strain-specific rosette disruption by glycosaminoglycans and sulfated glycoconjugates
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DOI:
10.1006/expr.1998.4349
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发表时间:
1999-02-01
影响因子:
2.1
通讯作者:
Carlson, J
Carlson, J
中科院分区:
医学4区
文献类型:
--
作者:
Barragan, A;Spillmann, D;Carlson, J

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重置,即恶性疟原虫感染的红细胞与未感染的红细胞的粘附,是一种与严重疟疾(例如脑型疟疾)的发生相关的剧毒寄生虫表型。具有特定抗重置活性的化合物是潜在的治疗剂。糖胺聚糖和硫酸化糖复合物被发现以菌株和分离株特异性的方式破坏玫瑰花结。玫瑰花结的破坏与肝素/硫酸乙酰肝素中 N-硫酸基团的存在密切相关,如改良肝素制剂所证明的。这一发现得到了来自含有 N-硫酸化葡萄糖胺的肝素/硫酸乙酰肝素的单糖和二糖对玫瑰花结的破坏的证实。此外,对被 FCR3S1(以及某种程度上 TM 284)恶性疟原虫菌株感染的红细胞培养物进行肝素酶 III 处理消除了重置。在与感染的培养物混合之前对未感染的红细胞进行肝素酶 III 处理,阻碍了玫瑰花结的形成,表明重置受体至少部分具有糖胺聚糖性质,(C) 1999 年学术出版社。
Resetting, the adhesion of Plasmodium falciparum-infected erythrocytes to uninfected erythrocytes, is a virulent parasite phenotype associated with the occurrence of severe malaria, e.g., cerebral malaria. Compounds with specific anti-resetting activity are potential therapeutic agents. Glycosaminoglycans and sulfated glycoconjugates were found to disrupt rosettes in a strain- and isolate-specific manner. Rosette disruption was strongly connected to the presence of N-sulfate groups in heparin/heparan sulfate as demonstrated by modified heparin preparations. This finding was corroborated by the disruption of rosettes with mono- and disaccharides derived from heparin/heparan sulfate that contained N-sulfated glucosamine. Furthermore, heparinase III treatment of erythrocyte cultures infected by FCR3S1 (and to some extent TM 284) P. falciparum strains abolished resetting. Heparinase III treatment of the uninfected erythrocytes prior to mixing with the infected culture impeded formation of rosettes, indicating that the resetting receptors at least partially are of glycosaminoglycan nature, (C) 1999 Academic Press.