GENETIC CONTROL OF FERRITIN SECRETION BY HUMAN MONONUCLE

人单核对铁蛋白分泌的遗传控制

• 批准号: 3153040
• 负责人: MARILYN S POLLACK
• 金额: $ 10.97万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-09-30 至 1986-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3153040
• 关键词: B lymphocyte; T lymphocyte; cell cell interaction; cell growth regulation; cell population study; cell type; congenital blood disorder; ferritin; genetic regulation; hemosiderosis; histocompatibility typing; immunohematology; iron disorder; iron metabolism; leukopoiesis; linkage mapping; major histocompatibility complex; membrane activity; monocyte; myelocyte; orphan disease /drug; plaque assay; secretion; tissue /cell culture

Since our group has shown that cells of the immune system protect against excess iron, that, in turn, iron and iron binding proteins have important effects on cells of the immune system, that the iron binding protein ferritin is synthesized and secreted by peripheral blood mononuclear cells, and that there are large HLA-associated individual variations in this ferritin secretion, we propose to study the cellular and genetic control of in vitro synthesis and secretion of ferritin by subpopulations of mononuclear cells (MNC). The proposed studies will utilize a modified hemolytic plaque assay with specific antibodies to acidic and basic ferritin isotypes, and "panning" and blocking techniques with monoclonal antibodies to MNC subpopulations and cell-surface determinants, in order: to determine the specific cell types involved in synthesis and secretion of ferritin by either activated on non-activated MNC; to determine the role of matching for HLA determinants in the cell-cell cooperation that occurs; to determine the relationship of particular MNC subpopulations to high" and "low" ferritin seretion; to determine the mechanism by which iron and cell activation induce in vitro ferritin synthesis and secretion; to determine individual variations in the production of ferritin-like factors that may inhibit myelopoiesis; to determine the specific basic and acidic isoferritin components of the ferritin secreted by different individuals; to determine whether quantitative differences in secretion from the cells of different individuals reflect variations in synthesis or variations in secretion only; to determine in studies of families whether or not these variations are inherited in linkage to the HLA complex; to study ferritin secretion in relation to genetic or acquired conditions of iron overload, such as hemochromatosis; and, to determine whether or not individual variations in other in vitro effects of iron on immunefucntion are also HLA associated and correlated with variations in ferritin secretion. These studies will collectively provide important information about the physiological role that cells of the immune system may play in the protection of tissue against potential toxicity from iron and about a mechanism by which genetic variations in the major histocompatibility complex may affect iron metabolism and the immune system itself.

因为我们的研究小组已经证明，免疫系统的细胞可以防止 过量的铁，反过来，铁和铁结合蛋白具有重要的 影响免疫系统的细胞，铁结合蛋白 铁蛋白由外周血单核细胞合成和分泌， 而且在这一过程中有很大的HLA相关的个体差异， 铁蛋白分泌，我们建议研究细胞和遗传控制的铁蛋白分泌， 铁蛋白的体外合成和分泌 单核细胞（MNC）。 拟议的研究将使用修改后的 用酸性和碱性特异性抗体进行溶血空斑试验 铁蛋白同种型，以及用单克隆抗体进行“淘选”和阻断技术， MNC亚群和细胞表面决定簇的抗体，顺序为： 以确定参与合成和分泌的特定细胞类型， 铁蛋白的活化对非活化的MNC;以确定的作用 在发生的细胞-细胞合作中匹配HLA决定簇; 确定特定MNC亚群与高”的关系， “低”铁蛋白分泌;以确定铁和细胞 激活诱导体外铁蛋白合成和分泌;以确定 铁蛋白样因子产生的个体差异， 抑制骨髓生成;确定特定的碱性和酸性 由不同个体分泌的铁蛋白的异铁蛋白组分; 以确定细胞分泌物的数量差异 不同个体之间的差异反映了合成的差异或 仅分泌;在家庭研究中确定这些 遗传变异与HLA复合体连锁;研究铁蛋白 与铁过载的遗传或获得性条件有关的分泌， 例如血色病;以及，为了确定个体是否 铁对免疫功能的其他体外作用的变化也是HLA 与铁蛋白分泌的变化相关。 这些 这些研究将共同提供有关 免疫系统的细胞可能在免疫系统中发挥的生理作用。 保护组织免受铁的潜在毒性， 主要组织相容性基因变异的机制 复合物可能会影响铁代谢和免疫系统本身。