TRANSCELLULAR TRANSPORT OF IMMUNOGLOBULINS

免疫球蛋白的跨细胞转运

• 批准号: 3125053
• 负责人: Richard D. Rodewald
• 金额: $ 9.94万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-07-01 至 1987-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3125053
• 关键词: antiantibody; antibody formation; antibody specificity; biological models; brush border membrane; electron microscopy; gastrointestinal absorption /transport; immune complex; immunochemistry; immunoglobulin G; ion exchange chromatography; monoclonal antibody; mouse mammary tumor virus; newborn animals; passive transport; pinocytosis; radiotracer; receptor mediated endocytosis; small intestines

Further studies are proposed to detial the cellular mechanisms whereby maternal immunoglobulin G (IgG) is selectively transferred across the intestinal epithelium of neonatal rats and mice by receptor-mediated endocytosis. Individual projects are proposed to evaluate the consequences of both normal and abnormal transport function. (1) The movement of membrane components and sorting of vesicle contents will be analyzed during selective IgG endocytosis by intestinal cells in situ using a variety of ultrastructural tracers including IgG-tracer conjugates, cationic ferritin, labeled lectins and anti-brush border antibody conjugates. Possible effects of lysosomal and other metabolic inhibitors will be investigated. (2) The pH-dependent binding of labled IgG to its membrane receptors will be studied using both ultrastructural and 125-I assays with isolated brush borders and intact cells. Effects of assay conditions and various treatments on the association constant and number of binding sites will be evaluated. (3) Factors that might influence the movement of receptors on the apical cell surface and the formation of endocytic vesicles will be investigated using isolated brush borders and intestinal cell in vitro. (4) The ultrastructural mechanism of entry into the neonatal mouse of mammary tumor virus, a pathogen known to be transferred across the intestine during the suckling period, will be studied. The possible role of specific antibody in transport and infection will be evaluated.

建议进一步研究以确定细胞机制， 母体免疫球蛋白G（IgG）选择性地转移到 受体介导的新生大鼠和小鼠肠上皮细胞 内吞作用 提出了个别项目，以评估其后果 正常和异常的运输功能。 (1)的移动 膜成分和囊泡内容物的分类将在 使用多种方法原位通过肠细胞进行的选择性IgG内吞 超微结构示踪剂，包括IgG-示踪剂缀合物，阳离子铁蛋白， 标记的凝集素和抗刷状缘抗体缀合物。 可能 将研究溶酶体和其它代谢抑制剂的作用。 (2)标记的IgG与其膜受体的pH依赖性结合将 使用离体刷的超微结构和125-I测定进行研究 边界和完整的细胞。 试验条件和各种 对结合常数和结合位点数目的处理将是 评估。 (3)可能影响受体运动的因素 顶端细胞表面和内吞囊泡的形成将是 采用离体刷状缘和离体肠细胞进行研究。 (4)新生小鼠体内的超微结构机制 乳腺肿瘤病毒，一种已知可以通过乳腺癌转移的病原体， 在哺乳期的肠道，将进行研究。 可能发挥的作用 对特异性抗体在转运和感染中的作用进行评价。