Online citations, reference lists, and bibliographies.
← Back to Search

Regulation Of Transferrin Receptor Expression And Ferritin Content In Human Mononuclear Phagocytes. Coordinate Upregulation By Iron Transferrin And Downregulation By Interferon Gamma.

T. Byrd, M. Horwitz
Published 1993 · Medicine, Biology

Cite This
Download PDF
Analyze on Scholarcy
We have investigated the regulation of key human iron binding proteins in mononuclear phagocytes by IFN gamma and iron transferrin. In a previous study, we demonstrated that IFN gamma downregulates the expression on human monocytes of transferrin receptors, the major source of iron for the cell. In the present study, we show that IFN gamma 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 IFN gamma-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, IFN gamma treatment also results in decreased iron incorporation. IFN gamma-activated monocytes incorporated 33% less iron from 59Fe-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 IFN gamma-activated monocytes. Ferritin in IFN gamma-activated monocytes is saturated with approximately three times as much 59Fe 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 IFN gamma-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 IFN gamma.
This paper references
Oxidation-reduction and the molecular mechanism of a regulatory RNA-protein interaction.
M. Hentze (1989)
Elevated levels of circulating cachectin/tumor necrosis factor in patients with acquired immunodeficiency syndrome.
J. Lähdevirta (1988)
Ferritin: an interim review.
A. Jacobs (1985)
Purified blood monocytes from HIV 1-infected patients produce high levels of TNF alpha and IL-1.
P. Roux‐Lombard (1989)
Chelate Mediated Transfer of Iron from Transferrin to Desferrioxamine
S. Pollack (1976)
The pivotal role of ferritin in cellular iron homeostasis
E. Mattia (1988)
Interleukin - l
C. A. Dinarello (1984)
Iron-responsive elements: regulatory RNA sequences that control mRNA levels and translation.
J. Casey (1988)
Low molecular weight intracellular iron transport compounds.
A. Jacobs (1977)
Interleukin 1 induces ferritin heavy chain in human muscle cells.
Y. Wei (1990)
Parameters affecting the in vitro maturation of human monocytes to macrophages.
H. Maoz (1986)
Legionnaires' disease bacterium (Legionella pneumophila) multiples intracellularly in human monocytes.
M. Horwitz (1980)
Gamma-interferon modulates human monocyte/macrophage transferrin receptor expression.
R. Taetle (1988)
Binding of a cytosolic protein to the iron-responsive element of human ferritin messenger RNA.
T. Rouault (1988)
Interferon-gamma inhibits thyrotropin-induced thyroglobulin gene transcription in cultured human thyrocytes.
A. W. Kung (1990)
Subunit dimers in sheep spleen apoferritin. The effect on iron storage.
J. Mertz (1983)
Human serum induces maturation of human monocytes in vitro. Changes in cytolytic activity, intracellular lysosomal enzymes, and nonspecific esterase activity.
Musson Ra (1983)
Perspectives in iron metabolism.
C. Finch (1982)
Chloroquine inhibits the intracellular multiplication of Legionella pneumophila by limiting the availability of iron. A potential new mechanism for the therapeutic effect of chloroquine against intracellular pathogens.
T. Byrd (1991)
Induction of hypoferremia and modulation of macrophage iron metabolism by tumor necrosis factor.
X. Alvarez-Hernandez (1989)
Gamma interferon limits access of Listeria monocytogenes to the macrophage cytoplasm
D. Portnoy (1989)
Translational control during the acute phase response. Ferritin synthesis in response to interleukin-1.
J. Rogers (1990)
Killing of Mycobacterium tuberculosis within human monocytes: activation by cytokines and calcitriol
M. Denis (1991)
Recombinant human tumor necrosis factor depresses serum iron in mice.
T. Tanaka (1987)
Expression of isoferritins in peripheral blood lymphocytes: Effect of phytohaemagglutinin and iron
K. Pattanapanyasat (1989)
Role of iron in Trypanosoma cruzi infection of mice.
R. Lalonde (1984)
Differential regulation of iron regulatory element-binding protein(s) in cell extracts of activated lymphocytes versus monocytes-macrophages.
U. Testa (1991)
Low molecular weight intracellular iron transport compounds.
A. Jacobs (1977)
Structural relationship between an iron-regulated RNA-binding protein (IRE-BP) and aconitase: Functional implications
T. Rouault (1991)
Interferon gamma-activated human monocytes downregulate transferrin receptors and inhibit the intracellular multiplication of Legionella pneumophila by limiting the availability of iron.
T. Byrd (1989)
c-fos mRNA expression in macrophages is downregulated by interferon-gamma at the posttranscriptional level.
D. Radzioch (1991)
Ferritin in Normal Erythrocytes, Lymphocytes, Polymorphs, and Monocytes
M. Summers (1974)
Lactoferrin inhibits or promotes Legionella pneumophila intracellular multiplication in nonactivated and interferon gamma-activated human monocytes depending upon its degree of iron saturation. Iron-lactoferrin and nonphysiologic iron chelates reverse monocyte activation against Legionella pneumophi
T. Byrd (1991)
B. Beutler (1988)
Purified blood monocytes from HIV 1-infected patients induce high levels of TNFα and IL-1
P. Roux‐Lombard (1989)
Iron up-modulates the expression of transferrin receptors during monocyte-macrophage maturation.
U. Testa (1989)
The molecular cloning and characterization of murine ferritin heavy chain, a tumor necrosis factor-inducible gene.
S. Torti (1988)
Lactoferrin uptake by mononuclear phagocytes
T. F. Byrd (1991)
A specific mRNA binding factor regulates the iron-dependent stability of cytoplasmic transferrin receptor mRNA
E. Müllner (1989)
Modulation of macrophage iron metabolism by tumour necrosis factor and interleukin 1.
J. Brock (1989)
Cytoplasmic protein binds in vitro to a highly conserved sequence in the 5' untranslated region of ferritin heavy- and light-subunit mRNAs.
E. A. Leibold (1988)

This paper is referenced by
Iron metabolism in the anemia of chronic disease.
G. Weiss (2009)
Long-term donors versus non-donor men: Iron metabolism and the atherosclerotic process.
P. Riško (2018)
Intraphagosomal Mycobacterium tuberculosis Acquires Iron from Both Extracellular Transferrin and Intracellular Iron Pools
O. Olakanmi (2002)
Mechanism and Regulation of Mycobactin Fatty Acyl-AMP Ligase FadD33*
O. Vergnolle (2013)
Polyvalent Cationic Metals Induce the Rate of Transferrin-independent Iron Acquisition by HL-60 Cells*
O. Olakanmi (1997)
Iron status following trauma, excluding burns
D. Walsh (1996)
Antimicrobial mechanisms of macrophages
M. Shiloh (1992)
Chloroquine is therapeutic in murine experimental model of paracoccidioidomycosis.
L. A. Dias-Melicio (2007)
Acute-phase proteins during inflammatory reaction by bacterial infection: Fish-model
I. Charlie-Silva (2019)
Pathogenesis and Treatment of the Anemia of Chronic Disease
S. Krantz (1994)
Interferon-gamma polymorphisms and risk of iron deficiency and anaemia in Gambian children.
K. M. Abuga (2020)
Contemporary approaches to designing and evaluating vaccines against Chlamydia
J. Igietseme (2003)
Antibody regulation of T-cell immunity: implications for vaccine strategies against intracellular pathogens
J. Igietseme (2004)
Integrin‐mediated epithelial‐T cell interaction enhances nitric oxide production and increased intracellular inhibition of Chlamydia
J. Igietseme (1996)
Macrophages in resistance to candidiasis.
A. Vázquez-Torres (1997)
Evidence for a Role for Interleukin-17, Th17 Cells and Iron Homeostasis in Protective Immunity against Tuberculosis in Cynomolgus Macaques
A. Wareham (2014)
Environmental regulation of the growth, physiology and virulence of Legionella pneumophila
W. S. Mauchline (1996)
IFN-γ for Friedreich ataxia: present evidence.
M. Wells (2015)
Mechanisms of therapeutic activity for gallium.
L. Bernstein (1998)
Chlamydia Vaccines
J. Igietseme (2012)
Identification of Fur, Aconitase, and Other Proteins Expressed by Mycobacterium tuberculosis under Conditions of Low and High Concentrations of Iron by Combined Two-Dimensional Gel Electrophoresis and Mass Spectrometry
D. K. Wong (1999)
Transcriptional analysis of persistent Chlamydia pneumoniae infection in vitro
Laura Mannonen (2011)
Chemokine CXCL12 Induces Binding of Ferritin Heavy Chain to the Chemokine Receptor CXCR4, Alters CXCR4 Signaling, and Induces Phosphorylation and Nuclear Translocation of Ferritin Heavy Chain*
R. Li (2006)
Retinoic acid and iron metabolism: a step towards design of a novel antitubercular drug.
Surajit Chakraborty (2014)
Pathogenesis and treatment of anaemia of chronic disease.
G. Weiss (2002)
T cell responses to Chlamydia trachomatis.
Wendy P. Loomis (2002)
Alternative activation deprives macrophages of a coordinated defense program to Mycobacterium tuberculosis
A. Kahnert (2006)
Tumor necrosis factor alpha (TNFalpha) promotes growth of virulent Mycobacterium tuberculosis in human monocytes iron-mediated growth suppression is correlated with decreased release of TNFalpha from iron-treated infected monocytes.
T. Byrd (1997)
Some macrophages kill Listeria monocytogenes while others do not
S. Fleming (1997)
Hereditary hemochromatosis results in decreased iron acquisition and growth by Mycobacterium tuberculosis within human macrophages
O. Olakanmi (2007)
Differential nitric oxide (NO) production by macrophages from mice and guinea pigs infected with virulent and avirulent Legionella pneumophila serogroup 1
P. Rajagopalan-Levasseur (1996)
Microreview Immune-mediated control of Chlamydia infection
N. Roan (2007)
See more
Semantic Scholar Logo Some data provided by SemanticScholar