EXTRACELLULAR DEVELOPMENT IN VITRO OF MALARIA PARASITES

疟疾寄生虫的体外细胞外发育

• 批准号: 3566950
• 负责人: WILLIAM TRAGER
• 金额: $ 20万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1993-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3566950
• 关键词: Plasmodium falciparum; communicable disease transmission; erythrocyte membrane; fluorescence microscopy; host organism interaction; human tissue; immunological substance; intracellular parasitism; laboratory mouse; malaria; membrane proteins; microorganism culture; microorganism growth; monoclonal antibody; protein kinase

Many of the pathogenic protozoa are obligate intracellular parasites; they develop only within another living host cell. Examples are the human parasite Toxoplasma,sometimes responsible for serious congenital infection and recently of increased significance in AIDS patients, the cattle parasite Theileria parva, cause of East Coast fever and, most important, the malarial parasites. We would like to know the nature of this dependence on a living host cell. Has the parasite lost or suppressed certain biosynthetic capabilities, in this way gaining an energetic advantages? Does the host cell supply triggers for differentiation, in addition to essential nutrients? How much of the integrity of the host cell does the parasite require? One approach toward answering these and related questions is to attempt to replace the living host cell with an environment in which the parasite will develop extracellularly. Such initial extracellular development has been obtained with the invasive stages, the merozoites, of Plasmodium falciparum, the major human malarial parasite. In a medium based on concentrated red cell extracts, and supplemented with ATP and pyruvate, up to 20% of the erythrocytic merozoites show initial development into early rings, their viability indicated not only by their appearance in stained films but also by their uptake of Rhodamine 123. Studies are proposed to extend and improve upon this development. The extracellular forms differ from young rings of the same age that have been lysed out from their host erythrocytes in that they lack a parasitophorous membrane. Comparative studies of these forms at the ultrastructural level and with the use of monoclonal antibodies to the ring stage now developed will provide information on the nature of the parasitophorous membrane. The induction and development of gametocytes will also be studied with special reference to the possible role of protein kinases and to the basis for the recently discovered greater formation of gametocytes in younger erythro- cytes. Results of the proposed work will contribute to understanding the physiology of the erythrocytic stages of malarial parasites and will bear on fundamental problems in intracellular parasitism.

许多致病性原生动物都是债务性的细胞内寄生虫。他们 仅在另一个活宿主细胞内开发。例子是人类 寄生虫弓形虫，有时负责严重的先天性感染 牛最近对艾滋病患者的意义增加了 寄生虫Theileria parva，东海岸发烧的原因，最重要的是 疟原虫。我们想知道这种依赖的本质 在活的宿主细胞上。寄生虫丢失或抑制 生物合成能力，以这种方式获得充满活力的优势？ 除了 必需的营养素？宿主单元的完整性有多少 寄生虫需要吗？回答这些和相关问题的一种方法 是试图用一个环境替换活宿主单元 寄生虫将细胞外发育。这种初始细胞外 已经通过侵入性阶段（梅罗祖族）获得了发展 恶性疟原虫，主要的人类疟原虫。在中等基础上 在浓缩的红细胞提取物上，并补充ATP和丙酮酸， 高达20％ 早期的戒指，它们的生存能力不仅表明了它们的出现 染色的膜，但也是由于其对若丹明123的吸收。研究是 提议扩展和改进这一发展。细胞外 形式与已经从同一年龄的年轻戒指不同的形式不同 他们的宿主红细胞缺乏寄生膜。 这些形式在超微结构层面和 现在开发的单克隆抗体对环阶段的使用将 提供有关寄生膜性质的信息。这 还将与特殊的诱导和发展配子细胞进行研究 参考蛋白激酶的可能作用和 最近发现在年轻的erythro-中更大的配子细胞形成 细胞。拟议工作的结果将有助于理解 疟原虫的红细胞阶段的生理学，将承受 关于细胞内寄生虫的基本问题。