REGULATION OF TRANSFERRIN RECEPTOR EXPRESSION AND FERRITIN CONTENT IN HUMAN MONONUCLEAR PHAGOCYTES - COORDINATE UP-REGULATION BY IRON TRANSFERRIN AND DOWN-REGULATION BY INTERFERON-GAMMA
REGULATION OF TRANSFERRIN RECEPTOR EXPRESSION AND FERRITIN CONTENT IN HUMAN MONONUCLEAR PHAGOCYTES - COORDINATE UP-REGULATION BY IRON TRANSFERRIN AND DOWN-REGULATION BY INTERFERON-GAMMA
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DOI：
10.1172/jci116318
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发表时间：
1993-03-01
影响因子：
15.9
通讯作者：
HORWITZ, MA
中科院分区：
文献类型：
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作者：
BYRD, TF;HORWITZ, MA
我们研究了IFN γ和铁转铁蛋白对单核吞噬细胞中关键的人铁结合蛋白的调节。在先前的研究中，我们证明了IFN γ下调转铁蛋白受体的人单核细胞的表达，转铁蛋白受体是细胞铁的主要来源。在目前的研究中，我们表明，IFN γ也下调铁蛋白，在细胞中的主要铁储存蛋白的细胞内浓度。通过放射免疫测定，未活化的单核细胞的平均铁蛋白含量为361+/-107 fg/单核细胞（平均值+/-SEM），而IFN γ活化的单核细胞的平均铁蛋白含量为64+/-13 fg/单核细胞，活化后降低82%（P < 0.01，t检验）。与其对这些铁蛋白的下调作用一致，IFN γ处理也导致铁掺入减少。IFN γ激活的单核细胞从Fe-59-转铁蛋白掺入的铁比未激活的单核细胞少33%（P < 0.05，t检验）。凝胶过滤色谱法显示，纳入铁主要位于铁蛋白在非活化和IFN γ活化的单核细胞。IFN γ激活的单核细胞中铁蛋白所饱和的Fe-59是未激活的单核细胞中铁蛋白的3倍。我们还探讨了铁转铁蛋白对人单核细胞转铁蛋白受体表达和细胞内铁蛋白含量的影响。我们已经发现铁转铁蛋白显著上调转铁蛋白受体表达和细胞内铁蛋白含量，（分别为2.3倍和1.3倍）和IFN γ激活的（3.4和2.9倍，）该研究表明，人单核细胞中的转铁蛋白受体表达和细胞内铁蛋白含量被铁转铁蛋白和铁蛋白受体单向和协调地上调。受IFN γ的单向和协同下调。
We have investigated the regulation of key human iron binding proteins in mononuclear phagocytes by IFNgamma and iron transferrin. In a previous study, we demonstrated that IFNgamma down-regulates the expression on human monocytes of transferrin receptors, the major source of iron for the cell. In the present study, we show that IFNgamma also downregulates the intracellular concentration of ferritin, the major iron storage protein in the cell. By radioimmunoassay, the mean ferritin content of nonactivated monocytes was 361+/-107 fg/monocyte (mean+/-SEM) whereas the mean ferritin content of IFNgamma-activated monocytes was 64+/-13 fg/monocyte, an 82% reduction with activation (P < 0.01, t test). Consistent with its downregulating effect on these iron proteins, IFNgamma treatment also results in decreased iron incorporation. IFNgamma-activated monocytes incorporated 33% less iron from Fe-59-transferrin than nonactivated monocytes (P < 0.05, t test). Gel filtration chromatography revealed that incorporated iron is located primarily in ferritin in both nonactivated and IFNgamma-activated monocytes. Ferritin in IFNgamma-activated monocytes is saturated with approximately three times as much Fe-59 as ferritin in nonactivated monocytes.We have also explored the effect of iron transferrin on transferrin receptor expression and intracellular ferritin content in human monocytes. We have found that iron transferrin markedly upregulates both transferrin receptor expression and intracellular ferritin content in both nonactivated (2.3- and 1.3-fold, respectively) and IFNgamma-activated (3.4- and 2.9-fold, respectively) monocytes.This study demonstrates that transferrin receptor expression and intracellular ferritin content in human monocytes is unidirectionally and coordinately upregulated by iron transferrin and unidirectionally and coordinately downregulated by IFNgamma.