GENETIC CONTROL OF FERRITIN SECRETION BY HUMAN MONONUCLE

因为我们的团队已经证明了免疫系统的细胞可以防止 过量的铁，进而，铁和铁结合蛋白具有重要的 对免疫系统细胞的影响，即铁结合蛋白 铁蛋白由外周血单核细胞合成和分泌， 其中有大量与人类白细胞抗原相关的个体变异 铁蛋白的分泌，我们建议研究细胞和遗传控制。 亚种群铁蛋白的体外合成和分泌 单个核细胞(MNC)。拟议的研究将利用修改后的 酸性和碱性特异性抗体的溶血空斑试验 铁蛋白亚型，以及用单克隆化的“淘洗”和阻断技术 针对单个核细胞亚群和细胞表面决定簇的抗体，顺序如下： 确定参与合成和分泌的特定细胞类型 铁蛋白通过激活对未激活的MNC；以确定其作用 在发生的细胞-细胞合作中匹配人类白细胞抗原决定簇； 确定特定MNC亚群与HIGH的关系“和 “低”铁蛋白血清；以确定铁和细胞 激活诱导体外铁蛋白合成和分泌；测定 铁蛋白样因子产生的个体差异可能 抑制骨髓生成；测定特定的碱性和酸性 不同个体分泌的铁蛋白的异铁蛋白成分； 为了确定细胞分泌的数量差异是否 不同个体的差异反映了合成的差异或 仅分泌；在对家庭的研究中确定这些 变异是遗传的，与人类白细胞抗原复合体有关；研究铁蛋白 与遗传性或获得性铁超载条件有关的分泌物， 例如血色沉着症；以及确定个人是否 铁在体外对免疫功能的其他影响的变化也是人类白细胞抗原 与铁蛋白分泌的变化有关和相关。这些 研究将共同提供关于 免疫系统的细胞在体内可能发挥的生理作用 保护组织免受铁和大约一种 主要组织亲和性遗传变异的机制 复合体可能会影响铁代谢和免疫系统本身。

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.