ERYTHROCYTE-ENDOTHELIAL INTERACTIONS IN MALARIA

疟疾是人类的一种血液疾病， 每年有100万例，仅在非洲， 百万死亡 为了根除这些疾病， 疾病，但成功仍然难以捉摸的原因有几个： 抗药性寄生虫的出现， 对杀虫剂的抗药性，缺乏有效的疫苗， 经济限制。 感染恶性疟原虫，是最致命的 人类疟疾的特征是 寄生在组织毛细血管和小静脉中的红细胞， 一种叫做寄生虫隔离的疾病 的附接 感染的红细胞对血管内皮的作用可能是一种重要的 自隔离以来，这种寄生虫的病理学原因 脑内血管可能会产生血管阻塞， 微血管血流，导致器官梗死，最终可能 导致脑型疟疾。 生物学意义和 红细胞内皮细胞粘附的生化机制 是未知的。 本研究旨在确定 人红细胞表面的分子因子和 内皮细胞负责粘附，从而提供 这是替代治疗策略的基础， 可用于治疗脑型疟疾。 体外 红细胞粘附的放射性测定已经开发出来， 用于评估固定、钙负荷和 酶处理对感染细胞的细胞粘附的影响。 隔离 将涉及放射性标记 SDS/ PAGE、免疫沉淀、蛋白质印迹和 cDNA文库的构建。 内皮细胞在血管生成中的作用 粘附过程将通过微丝来研究 破坏，细胞固定，并通过确定的影响， 在体外添加已知会影响 炎症反应。

Malaria, a blood disease of humans, is responsible for over 200 million cases annually, and in Africa alone causes greater than a million deaths. Much effort has been expended to eradicate the disease, but success has remained elusive for a number of reasons: appearance of drug-resistant parasites, the development of vector resistance to insecticides, the absence of an effective vaccine and economic constraints. Infections with Plasmodium falciparum, the most deadly of all the human malarias, are characterized by a marked retention of parasitized erythrocytes in tissue capillaries and venules, a condition called parasite sequestration. The attachment of infected erythrocytes to the vascular endothelium may be an impor- tant cause of the pathology with this parasite since sequestration within the brain blood vessels may produce vasocclusions, impede microvascular blood flow, cause organ infarction and ultimately may result in cerebral malaria. The biological significance and the biochemical mechanisms of erythrocyte endothelial cell adherence are unknown. The present study is designed to identify the molecular factors on the surface of the human erythrocyte and the endothelial cell which are responsible for adhesion thus providing a basis for alternative therapeutic strategies which eventually may be useful in the treatment of cerebral malaria. An in vitro radiometric assay for red cell adhesion has been developed and will be used to assess the effects of fixation, calcium loading, and enzyme treatment on the cytoadherence of infected cells. Isolation of the putative adhesion substance(s) will involve radiolabelling of cells, SDS/ PAGE, immunoprecipitation, Western blotting and construction of cDNA library. The role of the endothelial cell in the adhesion process will be investigated by microfilament disruption, cell fixation, and by determining the effects of the in vitro addition of pharmacologic agents known to affect the inflammatory response.