ERYTHROCYTE-ENDOTHELIAL INTERACTIONS IN MALARIA

疟疾是人类的一种血液疾病，导致200多人死亡 每年数以百万计的病例，仅在非洲就造成超过 百万人死亡。已经花费了大量的努力来根除这种 疾病，但由于一些原因，成功仍然难以捉摸： 耐药寄生虫的出现，媒介的发展 对杀虫剂的抗药性、缺乏有效的疫苗和 经济上的限制。 感染恶性疟原虫，是最致命的 人类疟疾的特点是显著地滞留在 组织毛细血管和小静脉内寄生的红细胞 一种称为寄生虫隔离的情况。依附于 感染红细胞到血管内皮细胞可能是一种障碍- 这种寄生虫自隔离以来病理的新原因 在脑血管内会产生血管闭塞，阻碍 微血管血流，导致器官梗塞，最终可能 导致脑型疟疾。它的生物学意义和 红细胞内皮细胞黏附的生化机制 都是未知的。本研究旨在确定 人红细胞表面分子因子及其与细胞免疫功能的关系 负责黏附的内皮细胞，从而提供 替代治疗策略的基础，最终可能 对治疗脑型疟疾有用。一种体外试验 已开发出红细胞黏附的放射分析方法，并将 用于评估固定、钙负荷和 酶处理对感染细胞细胞黏附的影响。隔离 推测的黏附物质(S)将涉及放射性标记 细胞计数、SDS/PAGE、免疫沉淀、Western blotting和 基因文库的构建。内皮细胞在血管内皮细胞中的作用 粘合过程将用微丝进行研究 破坏，细胞固定，并通过确定 在体外添加已知的影响药物的药物 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.