Barragan A, Spillmann D, Kremsner P G, Wahlgren M, Carlson J
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden.
Exp Parasitol. 1999 Feb;91(2):133-43. doi: 10.1006/expr.1998.4349.
Rosetting, 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-rosetting 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 rosetting. Heparinase III treatment of the uninfected erythrocytes prior to mixing with the infected culture impeded formation of rosettes, indicating that the rosetting receptors at least partially are of glycosaminoglycan nature.
红细胞凝聚，即恶性疟原虫感染的红细胞与未感染的红细胞黏附，是一种与严重疟疾（如脑型疟疾）发生相关的毒性寄生虫表型。具有特定抗红细胞凝聚活性的化合物是潜在的治疗药物。发现糖胺聚糖和硫酸化糖缀合物以菌株和分离株特异性的方式破坏红细胞凝聚。如改良肝素制剂所示，红细胞凝聚的破坏与肝素/硫酸乙酰肝素中N-硫酸基团的存在密切相关。这一发现得到了含有N-硫酸化葡糖胺的肝素/硫酸乙酰肝素衍生的单糖和二糖对红细胞凝聚破坏的证实。此外，用肝素酶III处理被FCR3S1（在一定程度上还有TM 284）恶性疟原虫菌株感染的红细胞培养物可消除红细胞凝聚。在与感染培养物混合之前，用肝素酶III处理未感染的红细胞会阻碍红细胞凝聚的形成，这表明红细胞凝聚受体至少部分具有糖胺聚糖性质。
