ERYTHROCYTE-ENDOTHELIAL INTERACTIONS IN MALARIA

疟疾中红细胞-内皮细胞的相互作用

• 批准号: 3564414
• 负责人: Irwin W Sherman
• 金额: $ 7.68万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1991-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3564414
• 关键词: calcium; cell adhesion; cell cell interaction; chemical binding; complementary DNA; diagnosis design /evaluation; erythrocytes; gel electrophoresis; genetic library; genetic manipulation; human subject; immunofluorescence technique; immunoprecipitation; inflammation; laboratory mouse; laboratory rabbit; malaria; membrane proteins; microfilaments; molecular cloning; molecular pathology; monoclonal antibody; protozoal antigen; radioimmunoassay; radiotracer; receptor; surface antigens; tissue /cell culture; vascular endothelium

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.

疟疾是人类的一种血液疾病，导致 200 多种疾病 每年有 100 多万个病例，仅在非洲就造成了超过 百万死亡。 为了消除这种现象，已经付出了很大的努力 疾病，但由于多种原因，成功仍然难以实现： 耐药寄生虫的出现，载体的发展 对杀虫剂产生抗药性，缺乏有效的疫苗 经济限制。 恶性疟原虫感染是最致命的 人类疟疾的特点是明显保留 组织毛细血管和小静脉中寄生的红细胞， 称为寄生虫隔离的情况。 附件为 受感染的红细胞对血管内皮可能是一个重要的 自隔离以来这种寄生虫的病理学的根本原因 脑血管内可能会产生血管闭塞，阻碍 微血管血流不畅，导致器官梗塞，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 未知。 本研究旨在确定 人体红细胞表面的分子因子及其 内皮细胞负责粘附，从而提供 替代治疗策略的基础，最终可能 可用于治疗脑型疟疾。 体外 红细胞粘附的放射测定法已经开发出来，并将 用于评估固定、钙负载和 酶处理对感染细胞细胞粘附的影响。 隔离 推定的粘附物质将涉及放射性标记 细胞、SDS/PAGE、免疫沉淀、蛋白质印迹和 cDNA文库的构建。 内皮细胞的作用 将通过微丝研究粘合过程 破坏，细胞固定，并通过确定的影响 体外添加已知影响的药物 炎症反应。