TY - JOUR
T1 - Rapid clearance of malaria circumsporozoite protein (CS) by hepatocytes
AU - Cerami, Carla
AU - Frevert, Ute
AU - Sinnis, Photini
AU - Takacs, Bela
AU - Nussenzweig, Victor
PY - 1994/2/1
Y1 - 1994/2/1
N2 - The circumsporozoite protein (CS) covers uniformly the plasma membrane of malaria sporozoites. In vitro, CS multimers bind specifically to regions of the hepatocyte plasma membrane that are exposed to circulating 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 acid sequence homology to a cell adhesive motif of thrombospondin. We have 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. Significant amounts of CS were not retained in any other organ. The striking parallelism between these in vitro and in vivo findings with the target specificity of malaria sporozoites, reinforces the hypothesis that the attachment of the parasites to hepatocytes is via region II-plus of CS.
AB - The circumsporozoite protein (CS) covers uniformly the plasma membrane of malaria sporozoites. In vitro, CS multimers bind specifically to regions of the hepatocyte plasma membrane that are exposed to circulating 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 acid sequence homology to a cell adhesive motif of thrombospondin. We have 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. Significant amounts of CS were not retained in any other organ. The striking parallelism between these in vitro and in vivo findings with the target specificity of malaria sporozoites, reinforces the hypothesis that the attachment of the parasites to hepatocytes is via region II-plus of CS.
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U2 - 10.1084/jem.179.2.695
DO - 10.1084/jem.179.2.695
M3 - Article
C2 - 8294876
AN - SCOPUS:0028091279
SN - 0022-1007
VL - 179
SP - 695
EP - 701
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 2
ER -