RAPID CLEARANCE OF MALARIA CIRCUMSPOROZOITE PROTEIN (CS) BY HEPATOCYTES

The circumsporozoite protein (CS) covers uniformly the plasma membrane of malaria sporozoites. In vitro, CS multimers bind specifically to r egions of the hepatocyte plasma membrane that are exposed to circulati ng blood in the Disse space. The ligand is in the region II-plus of CS , an evolutionarily conserved stretch of the protein that has amino ac id sequence homology to a cell adhesive motif of thrombospondin. We ha ve now found that intravenously injected CS constructs bind rapidly to the basolateral surface of hepatocytes, provided that the recombinant proteins contain region II-plus, and that they are aggregated. Signif icant amounts of CS were not retained in any other organ. The striking parallelism between these in vitro and in vivo findings with the targ et specificity of malaria sporozoites, reinforces the hypothesis that the attachment of the parasites to hepatocytes is via region II-plus o f CS.