Newbold C I, Craig A G, Kyes S, Berendt A R, Snow R W, Peshu N, Marsh K
Molecular Parasitology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, U.K.
Ann Trop Med Parasitol. 1997 Jul;91(5):551-7. doi: 10.1080/00034989760923.
The virulence of Plasmodium falciparum relative to the other species of malarial parasite which infect humans is thought to be due to this parasite's ability to adhere to endothelial cells lining small blood vessels and, in some cases, to its ability to form rosettes with uninfected erythrocytes. The latter phenotype has been found more frequently in cases of severe disease. The former property means that only the younger, asexual, intra-erythrocytic forms circulate whereas the more mature developmental stages are sequestered in the vasculature of a variety of organs. When large numbers of parasites accumulate in a vulnerable target organ such as the brain, the the life-threatening condition of cerebral malaria may result. While the factors that control whether or not cerebral malaria develops are not clearly defined, one crucial determinant my be the endothelial receptors utilised by the infecting isolate. Many such receptors have been identified, including CD36, thrombospondin, ICAM-1, VCAM, E-selectin and chondroitin-4-sulphate. The results of laboratory, field, post-mortem and direct receptor-binding studies indicate that, of the receptors currently identified, ICAM-1 binding is more likely to be associated with the development of cerebral malaria. The molecule expressed on the surface of the infected erythrocyte which mediates adherence to endothelium belongs to a large family of clonally variable antigens encoded by the var genes. The evidence for this conclusion and progress in defining the regions of var-gene products responsible to receptor-specific binding are discussed. Finally, the organization of the var genes within and between parasites is discussed in relation to the evolution of the var-gene family and its functions of antigenic variation and endothelial adhesion.
恶性疟原虫相对于其他感染人类的疟原虫的毒力，被认为是由于这种寄生虫能够黏附于小血管内衬的内皮细胞，并且在某些情况下，还由于其能够与未感染的红细胞形成花结。后一种表型在严重疾病病例中更为常见。前一种特性意味着只有较年轻的、无性的、红细胞内期形式在循环，而更成熟的发育阶段则被隔离在各种器官的脉管系统中。当大量寄生虫在诸如大脑等易损靶器官中积聚时，可能会导致危及生命的脑型疟疾。虽然控制脑型疟疾是否发生的因素尚未明确界定，但一个关键的决定因素可能是感染菌株所利用的内皮受体。已经鉴定出许多这样的受体，包括CD36、血小板反应蛋白、细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子（VCAM）、E-选择素和硫酸软骨素-4。实验室、现场、尸检和直接受体结合研究的结果表明，在目前鉴定出的受体中，ICAM-1结合更有可能与脑型疟疾的发生相关。介导与内皮细胞黏附的感染红细胞表面表达的分子属于由var基因编码的一大类克隆可变抗原家族。讨论了这一结论的证据以及在确定var基因产物负责受体特异性结合的区域方面取得的进展。最后，结合var基因家族的进化及其抗原变异和内皮黏附功能，讨论了寄生虫内部和之间var基因的组织情况。
