Cerami C, Frevert U, Sinnis P, Takacs B, Nussenzweig V
Department of Pathology, New York University Medical Center, New York 10016.
J Exp Med. 1994 Feb 1;179(2):695-701. doi: 10.1084/jem.179.2.695.
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.
环子孢子蛋白（CS）均匀覆盖疟原虫子孢子的质膜。在体外，CS多聚体特异性结合肝细胞质膜中暴露于狄氏间隙循环血液的区域。配体位于CS的II +区，这是该蛋白质一段进化保守的区域，与血小板反应蛋白的细胞粘附基序具有氨基酸序列同源性。我们现在发现，静脉注射的CS构建体能够迅速结合到肝细胞的基底外侧表面，前提是重组蛋白包含II +区且它们是聚集的。大量的CS不会保留在任何其他器官中。这些体外和体内研究结果与疟原虫子孢子的靶标特异性之间惊人的平行关系，强化了寄生虫通过CS的II +区附着于肝细胞的假说。
