CELL-SURFACE GLYCOSAMINOGLYCANS ARE NOT OBLIGATORY FOR PLASMODIUM-BERGHEI SPOROZOITE INVASION IN-VITRO

The malaria circumsporozoite (CS) protein binds to glycosaminoglycan c hains from heparan sulfate proteoglycans present on the basolateral su rface of hepatocytes and hepatoma cells in vitro. When injected into m ice, CS protein is rapidly cleared from the blood circulation by hepat ocytes. The binding region for the HSPGs is the evolutionarily conserv ed region II-plus of the CS protein. Here we have asked whether the pr esence of glycosaminoglycans on the plasma membrane of target cells is required for sporozoite invasion in vitro. Two types of target cells were used: HepG2 cells, which are permissive for Plasmodium berghei sp orozoite development into mature exoerythrocytic forms, and CHO cells, in which the intracellular development of the parasites is arrested e arly after penetration. The invasion of mutant CHO cells expressing un dersulfated glycosaminoglycans or no glycosaminoglycans was only inhib ited 41-49% or 24-32%, respectively, in comparison to invasion of CHO- K1 cells. Previous cleavage of HepG2 surface membrane glycosaminoglyca ns with heparinase or heparitinase had no significant inhibitory effec t on subsequent P. berghei sporozoite invasion and EEF development in these cells, although the glycosaminoglycan lyase treatments removed o ver 80% of CS binding sites from the cell surface. These results sugge st that although the presence of glycosaminoglycans on the target cell surface enhances sporozoite invasion, glycosaminoglycans are not requ ired for sporozoite penetration or the development of exoerythrocytic forms in vitro.