MECHANISMS OF P FALCIPARUM MEROZOITE INVASION

恶性疟原虫裂殖子侵袭机制

• 批准号: 3444913
• 负责人: RUPERT K. SCHMIDT-ULLRICH
• 金额: $ 19.25万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3444913
• 关键词: Plasmodium falciparum; Raman spectrometry; communicable disease transmission; computer data analysis; erythrocyte membrane; erythrocytes; fluorescence microscopy; fluorescent dye /probe; human tissue; liposomes; malaria; membrane activity; membrane lipids; membrane potentials; microorganism culture; monoclonal antibody; sporogenesis; virulence

One of the essential events that facilitate the effective multiplication of Plasmodium in the peripheral represents the rapid reinvasion of erythrocytes by released merozoites. Despite extensive morphological studies the biochemical mechanisms of the merozoite-erythrocyte interaction and the nature of the newly-formed parasitopherous membrane are largely unknown. Most recent advances in single cell spectroscopy, available in our laboratory, combined with high resolution, chromatographic lipid analyses should allow us to examine the following problems: (1) large scale isolation and purification of infective merozoites; (2) study of the merozoite-acceptor membrane interaction using (a) erythrocytes, (b) sealed, pink erythrocyte ghosts, and (c) large unilamelar liposomes with incorporated glycophorin A and/or human erythrocyte band 3 protein. Arrest of the merozoite invasion at various phases. (3) Study of the merozoite-target interaction at the single cell level by (a) video-intensified fluorescence microscopy (VIFM); (b) laser Raman microprobe spectroscopy, both linked to (c) computerized image analysis. (4) Use of fluorescent probes and VIFM to evaluate (a) state and distribution of membrane lipids and (b) transmembrane potential, intracellular pH and [Ca2+]. (5) Use of Raman microprobe to examine lipids using (a) deuterated lipid probes and (b) carotenoid probes. (6) Employment of radiolabeled target membrane phospholipids/cholesterol to measure (a) possible phospholipase activation and/or (b) cholesterol exchange.

促进有效乘法的基本事件之一 外周中的疟原虫代表着快速重新攻击 释放的蛋白酶的红细胞。 尽管形态广泛 研究merozoite-enthrocyte相互作用的生化机制 新形成的寄生膜的性质在很大程度上是 未知。 单细胞光谱法的最新进展，可在 我们的实验室，结合高分辨率，色谱脂质 分析应允许我们检查以下问题：（1）大型 感染性泌尿生组的尺度分离和纯化； （2）研究 使用（a）红细胞，（b）密封的蛋白石 - 受体膜相互作用， 粉红色的红细胞鬼，（c）大型Unilamelar脂质体带有 掺入的糖蛋白A和/或人类红细胞带3蛋白。 逮捕 在各个阶段的Merozoite入侵。 （3）研究 通过（a）在单细胞水平上的merozoite-target相互作用 视频强化的荧光显微镜（VIFM）； （b）激光拉曼 微型探针光谱均与（c）计算机图像分析相关联。 （4）使用荧光探针和VIFM评估（a）状态和 膜脂质的分布和（b）跨膜电势， 细胞内pH和[Ca2+]。 （5）使用拉曼微探针检查脂质 使用（a）剥离的脂质探针和（b）类胡萝卜素探针。 （6） 放射标记的靶膜磷脂/胆固醇的使用 测量（a）可能的磷脂酶激活和/或（b）胆固醇 交换。