van Berkel T J, Dekker C J, Kruijt J K, van Eijk H G
Department of Biochemistry I, Erasmus University Rotterdam, The Netherlands.
Biochem J. 1987 May 1;243(3):715-22. doi: 10.1042/bj2430715.
Rat transferrin or asialotransferrin doubly radiolabelled with 59Fe and 125I was injected into rats. A determination of extrahepatic and hepatic uptake indicated that asialotransferrin delivers a higher fraction of the injected 59Fe to the liver than does transferrin. In order to determine in vivo the intrahepatic recognition sites for transferrin and asialotransferrin, the liver was subfractionated into parenchymal, endothelial and Kupffer cells by a low-temperature cell isolation procedure. High-affinity recognition of transferrin (competed for by an excess of unlabelled transferrin) is exerted by parenchymal cells as well as endothelial and Kupffer cells with a 10-fold higher association (expressed per mg of cell protein) to the latter cell types. In all three cell types iron delivery occurs, as concluded from the increase in cellular 59Fe/125I ratio at prolonged circulation times of transferrin. It can be calculated that parenchymal cells are responsible for 50-60% of the interaction of transferrin with the liver, 20-30% is associated with endothelial cells and about 20% with Kupffer cells. For asialotransferrin a higher fraction of the injected dose becomes associated with parenchymal cells as well as with endothelial and Kupffer cells. Competition experiments in vivo with various sugars indicated that the increased interaction of asialotransferrin with parenchymal cells is specifically inhibited by N-acetylgalactosamine whereas mannan specifically inhibits the increased interaction of asialotransferrin with endothelial and Kupffer cells. Recognition of asialotransferrin by galactose receptors from parenchymal cells or mannose receptors from endothelial and Kupffer cells is coupled to active 59Fe delivery to the cells. It is concluded that, as well as parenchymal cells, liver endothelial and Kupffer cells are also quantitatively important intrahepatic sites for transferrin and asialotransferrin metabolism, an interaction exerted by multiple recognition sites on the various cell types.
将用59Fe和125I双重放射性标记的大鼠转铁蛋白或去唾液酸转铁蛋白注入大鼠体内。肝外和肝脏摄取的测定表明，与转铁蛋白相比，去唾液酸转铁蛋白将注入的59Fe中更高比例的铁输送到肝脏。为了在体内确定转铁蛋白和去唾液酸转铁蛋白的肝内识别位点，通过低温细胞分离程序将肝脏亚分成实质细胞、内皮细胞和库普弗细胞。转铁蛋白的高亲和力识别（可被过量未标记转铁蛋白竞争）由实质细胞以及内皮细胞和库普弗细胞发挥，后两种细胞类型的结合（以每毫克细胞蛋白表示）比前者高10倍。从转铁蛋白循环时间延长时细胞59Fe/125I比值的增加可以得出结论，在所有这三种细胞类型中都发生了铁的输送。据计算，实质细胞负责转铁蛋白与肝脏相互作用的50 - 60%，20 - 30%与内皮细胞相关，约20%与库普弗细胞相关。对于去唾液酸转铁蛋白，注入剂量中更高比例的部分与实质细胞以及内皮细胞和库普弗细胞相关。体内用各种糖类进行的竞争实验表明，去唾液酸转铁蛋白与实质细胞增加的相互作用被N - 乙酰半乳糖胺特异性抑制，而甘露聚糖特异性抑制去唾液酸转铁蛋白与内皮细胞和库普弗细胞增加的相互作用。实质细胞的半乳糖受体或内皮细胞和库普弗细胞的甘露糖受体对去唾液酸转铁蛋白的识别与向细胞的活性59Fe输送相关。得出的结论是，除了实质细胞外，肝脏内皮细胞和库普弗细胞也是转铁蛋白和去唾液酸转铁蛋白代谢在数量上重要的肝内位点，这种相互作用由各种细胞类型上的多个识别位点发挥。
