マラリア重症化関連新規宿主因子としてのScavenger receptor Aの同定

Severe falciparum malaria such as cerebral malaria and severe anemia is leading causes of morbidity and mortality. Plasmodium falciparum-infected red blood cells (pRBC) adhere to the endothelial cells via receptors expressed on the surface of the endothelial cells, and sequester in the microvasculature of several organs. Severe anemia, which may be due to a number of factors including rupture of the pRBC and phagocytosis of pRBC, is another cause of death. However, the molecular mechanism underlying both the cytoadherence and erythrophagocytosis related with severe malaria is not completely understood. Here, we report that the pRBC bind to the class A scavenger receptor, scavenger receptor A (SR-A), which is expressed on the surface of the activated phagocytes. 　First, we confirmed mRNA expression of scavenger receptors in the various tissues of P. berghei ANKA-infected mice. The expression of SR-A mRNA in all tissues was enhanced for 7 days postinfection. We also confirmed mRNA expression of SR-A in the human macrophage cell line, THP-1 cells, cultivated with pRBC. SR-A mRNA expression in THP-1 cells with pRBCs was observed after 24 hr cultivation, but not RBCs. Then, to identify cytoadherence of pRBCs to SR-A, human SR-A cDNA was transfected to CHO cells (CHO-SR-A cells). pRBC adhered to the CHO-SR-A cells, but not to the CHO-mock cells. Interestingly, the cytoadherence of both mature stage and ring form pRBCs to the CHO-SR-A cells was observed. Anti-SR-A antibody, but not Anexin V, efficiently blocked the cytoadherence of the pRBC to the CHO-SR-A cells. 　These results may suggest that SR-A acts as a host factor related with cytoadherence of the pRBC, which contributes to our present understanding of the pathology of severe falciparum malaria.

研究紹介 (Research Report)