A PRIMATE MODEL FOR HUMAN CEREBRAL MALARIA - PLASMODIUM-COATNEYI-INFECTED RHESUS-MONKEYS
A PRIMATE MODEL FOR HUMAN CEREBRAL MALARIA - PLASMODIUM-COATNEYI-INFECTED RHESUS-MONKEYS
复制标题
DOI：
10.4269/ajtmh.1992.46.391
复制
发表时间：
1992-04-01
影响因子：
3.3
通讯作者：
WEBSTER, K
中科院分区：
文献类型：
--
作者：
AIKAWA, M;BROWN, A;WEBSTER, K
人脑型疟疾发病机制中的一个主要因素是通过隔离寄生的人红细胞（PRBC）而阻塞脑微血管。体外研究表明，PRBC在微血管中的隔离是通过PRBC上的旋钮与内皮细胞表面上的受体如CD 36、血小板反应蛋白（TSP）和细胞间粘附分子-1（ICAM-1）的附着来介导的。然而，由于脑疟疾尸检病例中的新鲜人脑组织不易获得，因此很难在体内验证这一理论。虽然已经提出了几种人类脑型疟疾的动物模型，但没有一种动物模型显示出与人类相似的病理学结果。为了建立脑型疟疾的动物模型，我们研究了感染灵长类疟原虫Coatneyi的恒河猴脑。我们的研究表明，PRBC隔离和细胞粘附的旋钮PRBC的内皮细胞在这些猴子的脑微血管。免疫组织化学分析显示PRBC隔离的脑微血管具有CD 36、TSP和ICAM-1。这些蛋白质在未感染的对照猴的脑微血管中不明显。因此，我们的研究首次表明，感染Coatneyi疟原虫的恒河猴可以作为研究人类脑型疟疾的灵长类动物模型。通过使用这种动物模型，我们可能能够评估预防人类脑型疟疾的疫苗开发策略。
A major factor in the pathogenesis of human cerebral malaria is blockage of cerebral microvessels by the sequestration of parasitized human red blood cells (PRBC). In vitro studies indicate that sequestration of PRBC in the microvessels is mediated by the attachment of knobs on PRBC to receptors on the endothelial cell surface such as CD36, thrombospondin (TSP), and intercellular adhesion molecule-1 (ICAM-1). However, it is difficult to test this theory in vivo because fresh human brain tissues from cerebral malarial autopsy cases are not easy to obtain. Although several animal models for human cerebral malaria have been proposed, none have shown pathologic findings that are similar to those seen in humans. In order to develop an animal model for human cerebral malaria, we studied brains of rhesus monkeys infected with the primate malaria parasite, Plasmodium coatneyi. Our study demonstrated PRBC sequestration and cytoadherence of knobs on PRBC to endothelial cells in the cerebral microvessels of these monkeys. Cerebral microvessels with sequestered PRBC were shown by immunohistochemical analysis to possess CD36, TSP, and ICAM-1. These proteins were not evident in the cerebral microvessels of uninfected control monkeys. Thus, our study indicates, for the first time, that rhesus monkeys infected with P. coatneyi can be used as a primate model to study human cerebral malaria. By using this animal model, we may be able to evaluate strategies for the development of vaccines to prevent human cerebral malaria.