Malarial proteins in erythrocyte adhesion and dyserthropoiesis

红细胞粘附和红细胞生成障碍中的疟疾蛋白

• 批准号: 7527247
• 负责人: anthony holder
• 金额: $ 24.05万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7527247
• 关键词: Plasmodium; anemia; erythrocytes; erythropoiesis; host organism interaction; human tissue; laboratory mouse; laboratory rabbit; malaria; proteins

This application is designed to address the molecular basis of malaria-associated anemia, one of the most prevalent and often life-threatening manifestations of infection with the malaria parasite. Hundreds of millions of people have clinical malaria infections every year and thus the impact of the disease on human health is profound. During the process by which the parasites invade erythrocytes to allow them to multiply within, parasite molecules bind to the surface of these cells. It is proposed that these molecules, which are also shed from the parasite, bind to uninfected erythrocytes in the infected host and promote the destruction and clearance of uninfected red blood cells, thus contributing to anemia. Furthermore it is proposed to test the hypothesis that specific antibodies to such molecules promote this clearance. Two molecular complexes consisting of abundant proteins that have been implicated in binding to host erythrocytes will be examined to define their structure, diversity and function. The components responsible for binding to red cells and their role in red blood cell invasion will be clarified. Their specific interactions with molecules of the erythrocyte membrane will be defined, and their pontential to exacerbate anemia examined in field-based studies. The properties of parasite lines in which specific genes, coding for components of one of these molecular complexes, have been deleted will be studied. The phenotype of these modified parasites may be expressed as a change of host cell specificity, or different growth rate, or in an alteration of the parasitehost balance. It is proposed that these genetically manipulated parasites can disturb the mechanisms that maintain the red cell equilibrium, leading to dysfunctional control of red cell numbers and consequent anemia. It will be important to establish whether molecules that are potential malaria vaccine candidates are also the targets of immune mechanisms that promote anemia.

该应用程序旨在解决疟疾相关贫血的分子基础， 疟疾寄生虫感染的流行和往往危及生命的表现。数亿 的人有临床疟疾感染，因此，该疾病对人类健康的影响， 深刻在寄生虫侵入红细胞并使其在其中繁殖的过程中， 寄生虫分子与这些细胞的表面结合。有人提出，这些分子，这也是 从寄生虫中脱落，与感染宿主中未感染的红细胞结合，促进破坏， 清除未感染的红细胞，从而导致贫血。此外，建议测试 这一假说认为，针对这些分子的特异性抗体促进了这种清除。双分子复合物 将检查由与宿主红细胞结合有关的丰富蛋白质组成的蛋白质， 确定其结构、多样性和功能。负责与红细胞结合的成分及其 在红细胞侵袭中的作用将被阐明。它们与红细胞分子的特异性相互作用 膜将被定义，并在实地研究中检查其加剧贫血的潜力。的 寄生虫系的特性，其中特定的基因，编码这些分子之一的成分， 复合物，已被删除将被研究。这些修饰的寄生虫的表型可能是 表现为宿主细胞特异性的变化，或不同的生长速率，或寄生宿主的改变 平衡有人提出，这些基因操纵的寄生虫可以扰乱机制， 维持红细胞平衡，导致红细胞数量控制功能失调， 贫血重要的是要确定作为潜在的疟疾疫苗候选物的分子是否 也是促进贫血的免疫机制的目标。