Chen Q, Barragan A, Fernandez V, Sundström A, Schlichtherle M, Sahlén A, Carlson J, Datta S, Wahlgren M
Microbiology and Tumor Biology Center, Karolinska Institutet, the Swedish Institute for Infectious Disease Control, S-171 77 Stockholm, Sweden.
J Exp Med. 1998 Jan 5;187(1):15-23. doi: 10.1084/jem.187.1.15.
Severe Plasmodium falciparum malaria is characterized by excessive sequestration of infected and uninfected erythrocytes in the microvasculature of the affected organ. Rosetting, the adhesion of P. falciparum-infected erythrocytes to uninfected erythrocytes is a virulent parasite phenotype associated with the occurrence of severe malaria. Here we report on the identification by single-cell reverse transcriptase PCR and cDNA cloning of the adhesive ligand P. falciparum erythrocyte membrane protein 1 (PfEMP1). Rosetting PfEMP1 contains clusters of glycosaminoglycan-binding motifs. A recombinant fusion protein (Duffy binding-like 1-glutathione S transferase; Duffy binding-like-1-GST) was found to adhere directly to normal erythrocytes, disrupt naturally formed rosettes, block rosette reformation, and bind to a heparin-Sepharose matrix. The adhesive interactions could be inhibited with heparan sulfate or enzymes that remove heparan sulfate from the cell surface whereas other enzymes or similar glycosaminoglycans of a like negative charge did not affect the binding. PfEMP1 is suggested to be the rosetting ligand and heparan sulfate, or a heparan sulfate-like molecule, the receptor both for PfEMP1 binding and naturally formed erythrocyte rosettes.
重症恶性疟原虫疟疾的特征是受感染和未受感染的红细胞在受影响器官的微脉管系统中过度滞留。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，是一种与重症疟疾发生相关的恶性寄生虫表型。在此，我们报告通过单细胞逆转录酶PCR和cDNA克隆鉴定出黏附配体恶性疟原虫红细胞膜蛋白1（PfEMP1）。形成红细胞凝聚的PfEMP1含有糖胺聚糖结合基序簇。发现一种重组融合蛋白（达菲结合样1-谷胱甘肽S转移酶；达菲结合样-1-GST）可直接黏附于正常红细胞，破坏自然形成的红细胞凝聚，阻止红细胞凝聚重新形成，并与肝素-琼脂糖基质结合。黏附相互作用可用硫酸乙酰肝素或从细胞表面去除硫酸乙酰肝素的酶来抑制，而其他酶或带有类似负电荷的类似糖胺聚糖则不影响结合。PfEMP1被认为是红细胞凝聚配体，而硫酸乙酰肝素或硫酸乙酰肝素样分子是PfEMP1结合和自然形成的红细胞凝聚的受体。
