BIOLOGICAL AND BIOCHEMICAL STUDIES OF ANTIGENS ON MALARIA-INFECTED RED CELLS

疟疾感染红细胞抗原的生物学和生化研究

• 批准号: 3960495
• 负责人: R J HOWARD
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3960495
• 关键词: Africa; Plasmodium falciparum; Plasmodium knowlesi; cell adhesion; cellular immunity; erythrocyte membrane; erythrocytes; host organism interaction; immunoelectron microscopy; intracellular parasitism; malaria; membrane activity; microorganism immunology; protozoal antigen; protozoal infection; surface antigens; tissue /cell culture; vascular endothelium

We are studying the structure and function of malarial proteins inserted into and though the membrane of erythrocytes infected with mature asexual malaria parasites and molecules on the endothelial cells involved in cytoadherence. Two very large (Mv about 300,000) P. falciparum proteins have been localized to the surface membrane of infected erythrocytes. One protein is exposed on the cell surface and appears to mediate attachment to endothelial cells. The other malarial protein is localized under the membrane at the knob protrusions which mediate cytoadherence. These proteins do not appear to be related structurally. A third P. falciparum protein of unusually high histidine content has also been localized to the submembrane material under knobs. The histidine-rich protein is a structural or functional component of knobs but does not directly confer cytoadherence. Immunoelectonmicroscopy studies of P. falciparum isolates from West African patients have shown that the isolate-specific and pan-specific cell surface epitopes defined by homologous and heterologous African sera are both localized on the knob protrusions. The potential role of thrombospondin as the host cell ligand for cytoadherence has been studied in more detail. The stage-specificity of attachment of infected cells to thrombospondin and trypsin-sensitivity of the infected cell surface component involved in attachment to this protein match the properties of attachment to endothelial cells. We have also shown that the domain of thrombospondin involved in heparin binding is not involved in attachment of infected erythrocytes. We have also sequenced two P. falciparum genes encoding proteins of extraordinary histidine content, one of which is exported through the host erythocyte surface membrane into the plasma.

我们正在研究插入的疟疾蛋白质的结构和功能 进入并穿过感染了成熟无性生殖细胞的红细胞膜 疟疾寄生虫和内皮细胞上的分子参与 细胞粘附 两个非常大的（Mv约300，000）恶性疟原虫蛋白质已被发现。 定位于受感染红细胞的表面膜。 一种蛋白质 暴露在细胞表面，并似乎介导附着到 内皮细胞 另一种疟疾蛋白位于 在介导细胞粘附的旋钮突起处的膜。 这些 蛋白质似乎在结构上不相关。 第三种恶性疟原虫 组氨酸含量异常高的蛋白质也被定位于 在旋钮下的亚膜材料。 富含组氨酸的蛋白质是 但不直接赋予 细胞粘附 西非恶性疟原虫分离株的免疫电镜研究 患者已经表明，分离物特异性和泛特异性细胞表面 由同源和异源非洲血清定义的表位都是 定位在旋钮突起上。 血小板反应蛋白作为宿主细胞配体的潜在作用 已经更详细地研究了细胞粘附。 的阶段特异性 感染细胞对血小板反应蛋白和胰蛋白酶的敏感性 感染的细胞表面成分与这种蛋白质的附着有关 与附着于内皮细胞的特性相匹配。 我们还 表明参与肝素结合的血小板反应蛋白结构域不是 参与感染红细胞的附着。 我们还测序了两个恶性疟原虫基因编码的蛋白质， 特别的组氨酸含量，其中之一是通过宿主输出的 细胞表面膜进入血浆。