SULFATED POLYANIONS INHIBIT INVASION OF ERYTHROCYTES BY PLASMODIAL MEROZOITES AND CYTOADHERENCE OF ENDOTHELIAL-CELLS TO PARASITIZED ERYTHROCYTES

Sulfated proteoglycans have been shown to be involved in the binding o f sporozoites of malaria parasites to hepatocytes. In this study, we h ave evaluated the effect of sulfated glycosaminoglycans on the invasio n of erythrocytes by Plasmodium falciparum merozoites and cytoadherenc e of parasitized erythrocytes (PRBC) to endothelial cells, Invasion of erythrocytes by HB3EC-6 (an HB3 line selected for high binding to end othelial cells) was inhibited by dextran sulfate 500K, dextran sulfate 5K, sulfatides, fucoidan, and heparin but not by chondroitin sulfate A, With the exception of sulfatides, the invasion-inhibitory effect wa s not mediated by killing of parasites, Cytoadherence of HB3EC-6 to hu man microvascular endothelial cells (HMEC-1) and HB3C32-6 (an HB3 line selected for high binding to C32 melanoma cells) to C32 melanoma cell s was also inhibited by these sulfated glycoconjugates. The highly sul fated dextran sulfate 500K had the highest inhibitory effect on both i nvasion and cytoadherence. Both unsulfated dextran 500K and hyaluronic acid had no significant effect on invasion or cytoadherence, whereas the positively charged protamine sulfate promoted cytoadherence, Becau se preincubation of PRBC with sulfated glycosaminoglycans and treatmen t of target cells with heparinase had no significant inhibition on cyt oadherence, it is unlikely that sulfated glycoconjugates are used dire ctly by endothelial cells as cytoadhesion receptors, In an in vivo exp eriment, we found that the administration of dextran sulfate 500K to C BA/Ca mice infected with Plasmodium berghei ANKA reduced parasitemia a nd delayed the death associated with anemia, These observations sugges t that sulfated polyanions inhibit the invasion of erythrocytes by mer ozoites and cytoadherence of PRBC to endothelial cells by increasing t he negative repulsive charge and sterically interfering with the ligan d-receptor interaction after binding to target cells.