Research of host molecules associated with the pathogenesis of severe malarial anemia

脑疟疾和严重贫血等严重恶性疟疾是发病率和死亡率的主要原因。恶性疟原虫感染的红细胞(PRBCs)通过表达于内皮细胞表面的受体与内皮细胞黏附，隔离在多个器官的微血管中。另一个死亡原因是严重贫血，这可能是由于多种因素造成的，包括红细胞破裂和红细胞吞噬。然而，与严重疟疾相关的细胞黏附和红细胞吞噬的分子机制尚不完全清楚。在这里，我们报道了pRBC与A类清道夫受体SR-A和Marco结合，表达在活化的吞噬细胞表面。为了确定pRBC与SR-A和Marco的细胞黏附，我们将人SR-A或Marco基因导入CHO细胞(CHO-SR-A或CHO-Marco细胞)。此外，我们还对这两个分子的几个突变体进行了筛选，以确定与pRBC黏附相关的位点。PBCs与CHO-SR-A和CHO-Marco细胞均有粘附性，但与CHO-MARCK细胞无粘附性。PRBC在两种清道夫受体中均未观察到SRCR结构域缺失突变体的黏附，提示SR-A和Marco可能是与pRBC细胞黏附相关的宿主因子，有助于我们目前对恶性疟疾发病机制的认识。

Severe falciparum malaria such as cerebral malaria and severe anemia is leading cause of morbidity and mortality. Plasmodium falciparum-infected red blood cells (pRBCs) adhere to the endothelial cells via receptors expressed on the surface of the endothelial cells, sequester in the microvasculature of several organs. Severe anemia which may be due to a number of factors including rupture of the pRBCs and phagocytosis of pRBCs 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 pRBCs bind to the class A scavenger receptors, SR-A and MARCO, which is expressed on the surface of the activated phagocytes.To identify the cytoadherence of pRBCs to SR-A and MARCO, human SR-A or MARCO cDNA was transfected to CHO cells (CHO-SR-A or CHO-MARCO cells). Furthermore, several mutants of both molecules were made to identify the sites related with pRBC adherence. pRBCs adhered to the both CHO- SR-A and CHO-MARCO cells, but not to the CHO-mock cells. The pRBC did not observed adherence to the deletion mutants of SRCR domain in both scavenger receptors.These results may suggest that both SR-A and MARCO acts as a host factor related with cytoadherence of the pRBCs, and contribute to our present understanding the pathology of severe falciparum malaria.