BLOCKING OF THE RECEPTOR-MEDIATED INVASION OF ERYTHROCYTES BY PLASMODIUM-KNOWLESI MALARIA WITH SULFATED POLYSACCHARIDES AND GLYCOSAMINOGLYCANS
BLOCKING OF THE RECEPTOR-MEDIATED INVASION OF ERYTHROCYTES BY PLASMODIUM-KNOWLESI MALARIA WITH SULFATED POLYSACCHARIDES AND GLYCOSAMINOGLYCANS
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DOI：
10.1111/j.1432-1033.1991.tb15767.x
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发表时间：
1991-02-14
期刊：
影响因子：
--
通讯作者：
MILLER, LH
中科院分区：
文献类型：
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作者：
DALTON, JP;HUDSON, D;MILLER, LH
诺氏疟原虫侵入人类红细胞需要Duffy血型抗原。 诺氏毕赤酵母裂殖子合成135-kDa多肽，其以受体样特异性结合Duffy抗原。 在这项研究中，我们表明，硫酸多糖岩藻依聚糖和葡聚糖硫酸盐抑制结合的135-kDa多肽的人达菲阳性和恒河猴红细胞，而硫酸软骨素不。 岩藻依聚糖和硫酸葡聚糖还阻断诺氏疟原虫裂殖子对人Duffy B和恒河猴红细胞的体外侵袭。 这些抑制剂对135-kDa多肽与人Duffy B红细胞结合的阻断作用强于与恒河猴红细胞结合的阻断作用，这与它们对裂殖子侵入人红细胞的抑制作用强于对裂殖子侵入恒河猴红细胞的抑制作用有关。具有相对低电荷密度的岩藻依聚糖在4 μ g/ml时阻断135-kDa多肽的结合，而高度带负电荷的硫酸软骨素即使在1 mg/ml的浓度下也不阻断结合。 此外，岩藻聚糖-琼脂糖凝胶结合并从寄生虫培养物上清液中去除135-kDa多肽，其选择性等于Duffy血型抗原的选择性。 岩藻依聚糖和硫酸葡聚糖上的带负电荷的硫酸基团以及它们所保持的构象可能模拟了结合135-kDa诺氏毕赤酵母多肽的达菲抗原上的带类似电荷的基团。
Invasion of human erythrocytes by Plasmodium knowlesi requires the Duffy blood group antigen. P. knowlesi merozoites synthesize a 135-kDa polypeptide which binds to the Duffy antigen with receptor-like specificity. In this study, we show that the sulfated polysaccharide fucoidan and the glycosaminoglycan dextran sulfate inhibit the binding of the 135-kDa polypeptide to human Duffy-positive and rhesus erythrocytes while the chondroitin sulfates do not. Fucoidan and dextran sulphate also blocked the in vitro invasion of human Duffy b and rhesus erythrocytes cells by P. knowlesi merozoites. These inhibitors were more effective at blocking the binding of the 135-kDa polypeptide to human Duffy b erythrocytes than to rhesus erythrocytes, which correlated with them having a greater inhibitory effect on invasion of merozoites into human than into rhesus erythrocytes.The blocking by these sulfated sugars is not related to charge density on the polysaccharides; fucoidan with a relatively low charge density blocks binding of the 135-kDa polypeptide at 4-mu-g/ml, while the highly negatively charged chondroitin sulfates do not block binding even at the concentration of 1 mg/ml. Furthermore, fucoidan-Sepharose bound and removed the 135-kDa polypeptide from parasite culture supernatants with a selectivity equal to that of the Duffy blood group antigen. The negatively charged sulfate groups on fucoidan and dextran sulfate and the conformation in which they are held possibly mimic similarly charged groups on the Duffy antigen which bind the 135-kDa P. knowlesi polypeptide.