Blocking of the receptor-mediated invasion of erythrocytes by Plasmodium knowlesi malaria with sulfated polysaccharides and glycosaminoglycans.
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 micrograms/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.
Dalton
J P
JP
Malaria Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda.
Hudson
D
D
Adams
J H
JH
Miller
L H
LH
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D016264:Dextran Sulfate / Q000494:pharmacology*; D004375:Duffy Blood-Group System; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology / Q000469:parasitology*; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008253:Macaca mulatta; D008288:Malaria / Q000097:blood* / Q000276:immunology; D010961:Plasmodium / Q000187:drug effects / Q000472:pathogenicity*; D011134:Polysaccharides / Q000494:pharmacology*
D001798:Blood Proteins; D004375:Duffy Blood-Group System; D006025:Glycosaminoglycans; D011134:Polysaccharides; D016264:Dextran Sulfate; C007789:fucoidan