Pasloske B L, Howard R J
Affymax Research Institute, Palo Alto, California 94304.
Annu Rev Med. 1994;45:283-95. doi: 10.1146/annurev.med.45.1.283.
Erythrocytes infected with mature stages of Plasmodium falciparum malaria adhere to vascular endothelial cells in postcapillary venules of several organs. In some patients, infected cells also form rosettes with uninfected erythrocytes. The special pathology of acute cerebral malaria appears to result from excessive adherence of infected cells in cerebral vessels coupled with occlusion of cerebral blood flow in microvessels by infected cell rosettes. Several endothelial cell proteins have been identified as potential receptors for infected erythrocyte adherence to vascular endothelium, including thrombospondin, CD36, intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1). The receptor on infected erythrocytes that mediates adhesion to endothelial cells has been identified as a very large malarial protein on infected cells called PfEMP1. PfEMP1 has been shown to bind to CD36 and thrombospondin in vitro. Antibody-mediated blockade or reversal of infected erythrocyte adherence to vascular endothelium is postulated not only to decrease the pathology of blood-stage malaria, but also to lead to infected cell destruction and clearance, especially in the spleen. PfEMP1 is therefore a prime candidate malarial protein for inclusion in a multicomponent asexual malaria vaccine.
感染恶性疟原虫成熟阶段的红细胞会黏附在多个器官毛细血管后微静脉的血管内皮细胞上。在一些患者中，被感染的细胞还会与未感染的红细胞形成玫瑰花结。急性脑型疟疾的特殊病理似乎是由于脑血管中被感染细胞的过度黏附，以及被感染细胞玫瑰花结导致微血管中脑血流阻塞所致。几种内皮细胞蛋白已被确定为被感染红细胞黏附血管内皮的潜在受体，包括血小板反应蛋白、CD36、细胞间黏附分子-1（ICAM-1）、血管黏附分子-1（VCAM-1）和内皮白细胞黏附分子-1（ELAM-1）。介导被感染红细胞与内皮细胞黏附的受体已被确定为被感染细胞上一种非常大的疟疾蛋白，称为恶性疟原虫红细胞膜蛋白1（PfEMP1）。PfEMP1在体外已被证明能与CD36和血小板反应蛋白结合。抗体介导的阻断或逆转被感染红细胞与血管内皮的黏附，不仅被认为可以减轻血源性疟疾的病理，还能导致被感染细胞的破坏和清除，尤其是在脾脏中。因此，PfEMP1是多组分无性疟疾疫苗的主要候选疟疾蛋白。
