TRANSFERRIN AND HEPATIC IRON METABOLISM

在铁的运输方面仅次于红细胞生成系统， 肝脏是储存这种必需金属的器官，用于 铁酶的合成是生命不可缺少的，并回收利用 从有感觉的红细胞的血红蛋白中分离出来。 也许是因为 铁在细胞间的连续双向流动 肝脏特别容易受到铁的有害影响 超载。 因此，铁代谢的几乎所有方面都可能是 在这个复杂的机构中进行研究。 我们的方法是在离体肝细胞中检测铁代谢， 肝细胞和枯否细胞，以获得更深的 理解铁在细胞和分子水平上的加工。 特别感兴趣的是转铁蛋白与肝脏的相互作用 细胞，该蛋白质充当铁供体到铁受体 当细胞在铁中执行其生理功能时 新陈代谢. 我们试图研究调节摄取的因素， 肝细胞释放铁，特异性的相对重要性 受体介导的和非特异性的液相途径 肝细胞从转铁蛋白摄取铁，事件和 枯否细胞获得铁的清除机制 在红细胞吞噬作用，和铁的细胞毒性时， 吞噬红细胞的枯否细胞摄取铁的负荷 超过了细胞清除这些重要的 而是有毒元素。 综合起来，这些研究可能会发现 在铁代谢紊乱的管理中的应用- 在最常见的，往往是最致残的， 人类的弊病

Second only to the erythropoietic system in its traffic of iron, the liver is an organ where this essential metal is stored, utilized for the synthesis of iron enzymes indispensable to life, and recycled from the hemoglobin of senscent erythrocytes. Perhaps because of the continuous and bidirectional flux of iron across its cells, the liver is particularly vulnerable to the noxious effects of iron overload. Thus, almost all aspects of iron metabolism may be studied in this complex organ. Our approach is to examine iron metabolism in isolated liver cells, both hepatocytes and Kupffer cells, in order to gain deeper understanding of iron processing at cellular and molecular levels. Of particular interest is the interaction of transferrin with liver cells, with the protein acting either as iron donor to iron acceptor as the cells carry out their physiological functions in iron metabolism. We seek to study factors modulating the uptake and release of iron by hepatocytes, the relative importance of specific receptor-mediated and non-specific fluid-phase pathways in the uptake of iron from transferrin by hepatocytes, events and mechanisms in the elimination of iron acquired by Kupffer cells engated in erythrophagocytosis, and the cytotoxicity of iron when the burden of iron taken by erythrophagocytosing Kupffer cells exceeds the capacity of the cells to purge themselves of this vital but toxic element. Taken together, these studies may find application in the management of disorders of iron metabolism - among the most common and often the most disabling of humankind's ills.