Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway
Abstract
The serum ferritin concentration is a clinical parameter measured widely for the differential diagnosis of anemia. Its levels increase with elevations of tissue iron stores and with inflammation, but studies on cellular sources of serum ferritin as well as its subunit composition, degree of iron loading and glycosylation have given rise to conflicting results. To gain further understanding of serum ferritin, we have used traditional and modern methodologies to characterize mouse serum ferritin. We find that both splenic macrophages and proximal tubule cells of the kidney are possible cellular sources for serum ferritin and that serum ferritin is secreted by cells rather than being the product of a cytosolic leak from damaged cells. Mouse serum ferritin is composed mostly of L-subunits, whereas it contains few H-subunits and iron content is low. L-subunits of serum ferritin are frequently truncated at the C-terminus, giving rise to a characteristic 17-kD band that has been previously observed in lysosomal ferritin. Taken together with the fact that mouse serum ferritin is not detectably glycosylated, we propose that mouse serum ferritin is secreted through the nonclassical lysosomal secretory pathway.
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IrpLyzCre(+) mice have markedly higher plasma ferritin.
“Of note, IrpLyzCre(+) mice display a marked increase in plasma ferritin concentration (Figure 1E), as predicted for animals with augmented macrophage ferritin expression (Cohen et al., 2010).”
From Iron Regulatory Proteins Mediate Host Resistance to Salmonella Infection (2015) · cites this paper as Cohen et al., 2010
Blood ferritin comes largely from macrophages.
“This result supports earlier work concluding that macrophages represent a major source of ferritin in the blood (Cohen et al., 2010).”
From Iron Regulatory Proteins Mediate Host Resistance to Salmonella Infection (2015) · cites this paper as Cohen et al., 2010
Cites
The ferritins: molecular properties, iron storage function and cellular regulation
Harrison, P. M., & Arosio, P. (1996) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(96)00022-9 · Cited by 2,667 · see citing works
Blott, E. J., & Griffiths, G. M. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm732 · Cited by 686 · see citing works
Binding and uptake of H-ferritin are mediated by human transferrin receptor-1
Li, L., Fang, C. J., Ryan, J. C., Niemi, E. C., Lebrón, J. A., Björkman, P. J., Arase, H., Torti, F. M., Torti, S. V., Nakamura, M. C., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913192107 · Cited by 558 · see citing works
A cytosolic iron chaperone that delivers iron to ferritin
Shi, H., Bencze, K. Z., Stemmler, T. L., & Philpott, C. C. (2008) · Science · doi:10.1126/science.1157643 · Cited by 536 · see citing works
LaVaute, T., Smith, S., Cooperman, S., Iwai, K., Land, W., Meyron-Holtz, E., Drake, S. K., Miller, G., Abu-Asab, M., Tsokos, M., et al. (2001) · Nature Genetics · doi:10.1038/84859 · Cited by 509 · see citing works
Levi, S., Luzzago, A., Cesareni, G., Cozzi, A., Franceschinelli, F., Albertini, A., & Arosio, P. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)81326-1 · Cited by 378 · see citing works
Scara5 Is a Ferritin Receptor Mediating Non-Transferrin Iron Delivery
Li, J. Y., Paragas, N., Ned, R. M., Qiu, A., Viltard, M., Leete, T., Drexler, I. R., Chen, X., Sanna‐Cherchi, S., Mohammed, F., et al. (2009) · Developmental Cell · doi:10.1016/j.devcel.2008.12.002 · Cited by 355 · see citing works
Jacobs, A., & Worwood, M. (1975) · New England Journal of Medicine · doi:10.1056/nejm197505012921805 · Cited by 353 · see citing works
Nichol, H., Law, J. H., & Winzerling, J. J. (2002) · Annual Review of Entomology · doi:10.1146/annurev.ento.47.091201.145237 · Cited by 279 · see citing works
Secretion of Ferritin by Rat Hepatoma Cells and Its Regulation by Inflammatory Cytokines and Iron
Tran, T. N., Eubanks, S. K., Schaffer, K. J., Zhou, C. Y. J., & Linder, M. C. (1997) · Blood · doi:10.1182/blood.v90.12.4979 · Cited by 236 · see citing works
TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis
Chen, T. T., Li, L., Chung, D.-H., Allen, C. D. C., Torti, S. V., Torti, F. M., Cyster, J. G., Chen, C.-Y., Brodsky, F. M., Niemi, E. C., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20042433 · Cited by 219 · see citing works
Ferritin: a novel mechanism for delivery of iron to the brain and other organs
Fisher, J., Devraj, K., Ingram, J., Slagle‐Webb, B., Madhankumar, A. B., Liu, X., Klinger, M., Simpson, I. A., & Connor, J. R. (2007) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00599.2006 · Cited by 206 · see citing works
Quintana, C., COWLEY, J. M., & Marhic, C. (2004) · Journal of Structural Biology · doi:10.1016/j.jsb.2004.03.001 · Cited by 189 · see citing works
Specific iron chelators determine the route of ferritin degradation
De Domenico, I., Ward, D. M., & Kaplan, J. (2009) · Blood · doi:10.1182/blood-2009-05-224188 · Cited by 176 · see citing works
Regulatory effects of ferritin on angiogenesis
Coffman, L. G., Parsonage, D., D'Agostino, R., Torti, F. M., & Torti, S. V. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812010106 · Cited by 168 · see citing works
Jiang, Y., Oliver, P. L., Davies, K. E., & Platt, N. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m507599200 · Cited by 154 · see citing works
Macrophages function as a ferritin iron source for cultured human erythroid precursors
Leimberg, M. J., Prus, E., Konijn, A. M., & Fibach, E. (2007) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21499 · Cited by 137 · see citing works
Regulated secretion of glycosylated human ferritin from hepatocytes
Ghosh, S., Hevi, S., & Chuck, S. L. (2003) · Blood · doi:10.1182/blood-2003-09-3050 · Cited by 130 · see citing works
Detection of a glycosylated subunit in human serum ferritin
Cragg, S. J., Wagstaff, M., & Worwood, M. (1981) · Biochemical Journal · doi:10.1042/bj1990565 · Cited by 126 · see citing works
Mizuno, M., & Singer, S. J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.12.5732 · Cited by 121 · see citing works
Zhang, D., Meyron‐Holtz, E. G., & Rouault, T. A. (2007) · Journal of the American Society of Nephrology · doi:10.1681/asn.2006080908 · Cited by 109 · see citing works
Detection and isolation of a hepatic membrane receptor for ferritin.
Mack, U., Powell, L. W., & Halliday, J. W. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)32470-0 · Cited by 108 · see citing works
Characterization of Serum Ferritin in Iron Overload: Possible Identity to Natural Apoferritin
Arosio, P., YOKOTA, M., & Drysdale, J. (1977) · British Journal of Haematology · doi:10.1111/j.1365-2141.1977.tb00640.x · Cited by 107 · see citing works
Worwood, M., & Cook, J. D. (1979) · CRC Critical Reviews in Clinical Laboratory Sciences · doi:10.3109/10408367909147133 · Cited by 104 · see citing works
High Levels of Ferritin and its Iron in Fetal Bovine Serum
Kakuta, K., Orino, K., Yamamoto, S., & Watanabe, K. (1997) · Comparative Biochemistry and Physiology Part A Physiology · doi:10.1016/s0300-9629(96)00403-3 · Cited by 96 · see citing works
Kannengiesser, C., Jouanolle, A., Hetet, G., Mosser, A., Muzeau, F., Henry, D., Bardou‐Jacquet, E., Mornet, M., Brissot, P., Deugnier, Y., et al. (2009) · Haematologica · doi:10.3324/haematol.2008.000125 · Cited by 85 · see citing works
Characterization and Distribution of Ferritin Binding Sites in the Adult Mouse Brain
Hulet, S. W., Hess, E. J., Debinski, W., Arosio, P., Bruce, K., Powers, S. K., & Connor, J. R. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.720868.x · Cited by 82 · see citing works
Smith, C. P., & Thévenod, F. (2008) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2008.10.010 · Cited by 80 · see citing works
Addison, G. M., Jacobs, A. J., Walters, G. O., & Worwood, M. (1973) · The Lancet · doi:10.1016/s0140-6736(73)90231-6 · Cited by 78 · see citing works
Aguilar‐Martinez, P., Schved, J., & Brissot, P. (2005) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2005.40998.x · Cited by 72 · see citing works
Santambrogio, P., Cozzi, A., Levi, S., & Arosio, P. (1987) · British Journal of Haematology · doi:10.1111/j.1365-2141.1987.tb02271.x · Cited by 70 · see citing works
Ferritin uptake by human erythroid precursors is a regulated iron uptake pathway
Gelvan, D., Fibach, E., Meyron-Holtz, E., & Konijn, A. (1996) · Blood · doi:10.1182/blood.v88.8.3200.bloodjournal8883200 · Cited by 62 · see citing works
Self-citationIron and ferritin in inflammation and cancer.
Torti, S. V., & Torti, F. M. (1994) · PubMed · Cited by 53 · see citing works
Ferring–Appel, D., Hentze, M. W., & Galy, B. (2008) · Blood · doi:10.1182/blood-2008-05-155093 · Cited by 53 · see citing works
Baraibar, M. A., Muhoberac, B. B., Garringer, H. J., Hurley, T. D., & Vidal, R. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.042986 · Cited by 52 · see citing works
Serum ferritin: Does it differ from tissue ferritin?
Linder, M. C., Schaffer, K. J., Hazegh-Azam, M., Zhou, C. Y. J., Tran, T. N., & Nagel, G. M. (1996) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.1996.tb00030.x · Cited by 44 · see citing works
Siderosomal ferritin. The missing link between ferritin and haemosiderin?
Andrews, S. C., Treffry, A., & Harrison, P. M. (1987) · Biochemical Journal · doi:10.1042/bj2450439 · Cited by 42 · see citing works
The Iron Content of Serum Ferritin: Physiological Importance and Diagnostic Value
ten Kate, J., Wolthuis, A. M., Westerhuis, B. W. J. J. M., & van Deursen, C. T. B. M. (1997) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.1997.35.1.53 · Cited by 31 · see citing works
Isolation and fractionation of ferritin from human term placenta—A source for human isoferritins
Konijn, A. M., Tal, R., Levy, R., & Matzner, Y. (1985) · Analytical Biochemistry · doi:10.1016/0003-2697(85)90135-6 · Cited by 30 · see citing works
Characterization of the ferritin receptors of human T lymphoid (MOLT-4) cells.
Moss, D., Powell, L. W., Arosio, P., & Halliday, J. W. (1992) · PubMed · Cited by 29 · see citing works
Iron speciation study in Hfe knockout mice tissues: Magnetic and ultrastructural characterisation
Gutiérrez, L., Quintana, C., Patiño, C., Bueno, J., Coppin, H., Roth, M. P., & Lázaro, F. J. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.03.007 · Cited by 26 · see citing works
Self-citationBinding and uptake of exogenous isoferritins by cultured human erythroid precursor cells
Meyron‐Holtz, E. G., Fibach, E., Gelvan, D., & Konijn, A. M. (1994) · British Journal of Haematology · doi:10.1111/j.1365-2141.1994.tb04797.x · Cited by 26 · see citing works
Biochemical properties of canine serum ferritin: iron content and nonbinding to concanavalin A
Watanabe, K., Muranishi, N., Murata, Y., Orino, K., Okano, S., & Yamamoto, S. (2000) · BioMetals · doi:10.1023/a:1009276323707 · Cited by 19 · see citing works
[New observations on the erythroblast islet and rhopheocytosis of ferritin].
BESSIS, M. C., & Breton-Gorius, J. (2000) · PubMed · Cited by 14 · see citing works
The diagnostic value of serum ferritin determinations for assessing iron status.
Worwood, M. (1987) · PubMed · Cited by 13 · see citing works
Ferritin synthesis on polyribosomes attached to the endoplasmic reticulum
Linder, M. C., Madani, N., Middleton, R. B., Miremadi, A., Cairo, G., Tacchini, L., Schiaffonati, L., & Rappocciolo, E. (1992) · Journal of Inorganic Biochemistry · doi:10.1016/0162-0134(92)84068-x · Cited by 12 · see citing works
Tacchini, L., Rappocciolo, E., Ferrero, M., Schiaffonati, L., & Cairo, G. (1992) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/0167-4781(92)90067-a · Cited by 12 · see citing works
Serum ferritin in type I diabetes
Carenini, A., Ronchi, D., Garbetta, F., Pozza, G., Gabri, E., Levi, S., & Arosio, P. (1985) · Clinica Chimica Acta · doi:10.1016/0009-8981(85)90187-1 · Cited by 12 · see citing works
Vaisman, B. L., Santambrogio, P., Arosio, P., Fibach, E., & Konijn, A. M. (1999) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.1999.022 · Cited by 7 · see citing works
Broxmeyer, H. E., Mantel, C., Gentile, P. S., Srivastava, C. H., Miyazawa, K., Zucali, J. R., Rado, T. A., Levi, S., & Arosio, P. (2015) · Current studies in hematology and blood transfusion · doi:10.1159/000419358 · Cited by 5 · see citing works
[The erythroblastic islet and the rhopheocytosis of ferritin in inflammation].
BESSIS, M. C., & Breton-Gorius, J. (1998) · PubMed · Cited by 5 · see citing works
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2 of the 53 references couldn’t be matched to a known paper.
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Iron and cancer: more ore to be mined
Torti, S. V., & Torti, F. M. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3495 · Cited by 1,621 · see citing works
Weiss, G., Ganz, T., & Goodnough, L. T. (2019) · Blood · doi:10.1182/blood-2018-06-856500 · Cited by 1,219 · see citing works
Ganz, T. (2013) · Physiological Reviews · doi:10.1152/physrev.00008.2013 · Cited by 1,122 · see citing works
Regulation of cellular iron metabolism
Wang, J., & Pantopoulos, K. (2011) · Biochemical Journal · doi:10.1042/bj20101825 · Cited by 986 · see citing works
Transferrin and transferrin receptors update
Kawabata, H. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.06.037 · Cited by 697 · see citing works
Association of inflammatory markers with the severity of COVID-19: A meta-analysis
Zeng, F., Huang, Y., Guo, Y., Yin, M., Chen, X., Liang, X., & Deng, G. (2020) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2020.05.055 · Cited by 666 · see citing works
Kell, D. B., & Pretorius, E. (2014) · Metallomics · doi:10.1039/c3mt00347g · Cited by 667 · see citing works
Drakesmith, H., Nemeth, E., & Ganz, T. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.09.006 · Cited by 638 · see citing works
Hyperferritinemia and inflammation
Kernan, K. F., & Carcillo, J. A. (2017) · International Immunology · doi:10.1093/intimm/dxx031 · Cited by 638 · see citing works
Hemophagocytic Lymphohistiocytosis
Al-Samkari, H. T., & Berliner, N. (2017) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-020117-043625 · Cited by 510 · see citing works
Iron metabolism in the CNS: implications for neurodegenerative diseases
Rouault, T. A. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3453 · Cited by 496 · see citing works
Rosário, C., Zandman‐Goddard, G., Meyron‐Holtz, E. G., D’Cruz, D. P., & Shoenfeld, Y. (2013) · BMC Medicine · doi:10.1186/1741-7015-11-185 · Cited by 466 · see citing works
Overview of iron metabolism in health and disease
Dev, S., & Babitt, J. L. (2017) · Hemodialysis International · doi:10.1111/hdi.12542 · Cited by 469 · see citing works
A comprehensive review on adult onset Still's disease
Giacomelli, R., Ruscitti, P., & Shoenfeld, Y. (2018) · Journal of Autoimmunity · doi:10.1016/j.jaut.2018.07.018 · Cited by 420 · see citing works
Macrophages and Iron Metabolism
Soares, M. P., & Hamza, I. (2016) · Immunity · doi:10.1016/j.immuni.2016.02.016 · Cited by 401 · see citing works
The struggle for iron - a metal at the host-pathogen interface: Iron at the host-pathogen interface
Nairz, M., Schroll, A., Sonnweber, T., & Weiss, G. (2010) · Cellular Microbiology · doi:10.1111/j.1462-5822.2010.01529.x · Cited by 398 · see citing works
Nemeth, E., & Ganz, T. (2014) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2014.04.005 · Cited by 401 · see citing works
Iron in infection and immunity
Nairz, M., & Weiss, G. (2020) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2020.100864 · Cited by 359 · see citing works
Targeting iron metabolism in drug discovery and delivery
Crielaard, B. J., Lammers, T., & Rivella, S. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.248 · Cited by 352 · see citing works
Dedicated SNAREs and specialized TRIM cargo receptors mediate secretory autophagy
Kimura, T., Jia, J., Kumar, S. G., Choi, S. W., Gu, Y., Mudd, M. H., Dupont, N., Jiang, S., Peters, R. S., Farzam, F., et al. (2016) · The EMBO Journal · doi:10.15252/embj.201695081 · Cited by 329 · see citing works
IL-1β/IL-6/CRP and IL-18/ferritin: Distinct Inflammatory Programs in Infections
Slaats, J., ten Oever, J., van de Veerdonk, F. L., & Netea, M. G. (2016) · PLoS Pathogens · doi:10.1371/journal.ppat.1005973 · Cited by 320 · see citing works
Iron metabolism: pathophysiology and pharmacology
Roemhild, K., von Maltzahn, F., Weiskirchen, R., Knüchel, R., von Stillfried, S. F., & Lammers, T. (2021) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2021.05.001 · Cited by 315 · see citing works
Evstatiev, R., & Gasché, C. (2011) · Gut · doi:10.1136/gut.2010.214312 · Cited by 292 · see citing works
Limitations of Serum Ferritin in Diagnosing Iron Deficiency in Inflammatory Conditions
Dignass, A. U., Farrag, K., & Stein, J. M. (2018) · International Journal of Chronic Diseases · doi:10.1155/2018/9394060 · Cited by 289 · see citing works
The multifaceted role of iron in renal health and disease
van Swelm, R. P. L., Wetzels, J. F. M., & Swinkels, D. W. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0197-5 · Cited by 279 · see citing works
Iron and liver fibrosis: Mechanistic and clinical aspects
Mehta, K. J., Farnaud, S., & Sharp, P. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i5.521 · Cited by 271 · see citing works
COVID-19 gone bad: A new character in the spectrum of the hyperferritinemic syndrome?
Colafrancesco, S., Alessandri, C., Conti, F., & Priori, R. (2020) · Autoimmunity Reviews · doi:10.1016/j.autrev.2020.102573 · Cited by 272 · see citing works
From the Cradle to the Grave: The Role of Macrophages in Erythropoiesis and Erythrophagocytosis
Klei, T. R. L., Meinderts, S. M., van den Berg, T. K., & van Bruggen, R. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00073 · Cited by 262 · see citing works
Habib, H. M., Ibrahim, S., Zaim, A., & Ibrahim, W. H. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111228 · Cited by 253 · see citing works
Oxidative Stress and the Homeodynamics of Iron Metabolism
Bresgen, N., & Eckl, P. (2015) · Biomolecules · doi:10.3390/biom5020808 · Cited by 247 · see citing works
The significance of ferritin in cancer: Anti-oxidation, inflammation and tumorigenesis
Alkhateeb, A. A., & Connor, J. R. (2013) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2013.07.002 · Cited by 246 · see citing works
Serum ferritin as an indicator of iron status: What do we need to know?
Daru, J., Colman, K., Stanworth, S. J., De La Salle, B., Wood, E. M., & Pasricha, S.-R. (2017) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.117.155960 · Cited by 246 · see citing works
Fernández‐Real, J. M., McClain, D. A., & Manco, M. (2015) · Diabetes Care · doi:10.2337/dc14-3082 · Cited by 235 · see citing works
Ferritin is secreted via 2 distinct nonclassical vesicular pathways
Truman-Rosentsvit, M., Berenbaum, D., Spektor, L., Cohen, L. A., Belizowsky-Moshe, S., Lifshitz, L., Ma, J., Li, W., Kesselman, E., Abutbul-Ionita, I., et al. (2018) · Blood · doi:10.1182/blood-2017-02-768580 · Cited by 223 · see citing works
Chemistry and biology of ferritin
Plays, M., Müller, S., & Rodriguez, R. (2021) · Metallomics · doi:10.1093/mtomcs/mfab021 · Cited by 232 · see citing works
NCOA4-Mediated Ferritinophagy: A Potential Link to Neurodegeneration
Quiles del Rey, M., & Mancias, J. D. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00238 · Cited by 227 · see citing works
Marked hyperferritinemia does not predict for HLH in the adult population
Schram, A. M., Campigotto, F., Mullally, A., Fogerty, A. E., Massarotti, E. M., Neuberg, D. S., & Berliner, N. (2015) · Blood · doi:10.1182/blood-2014-10-602607 · Cited by 222 · see citing works
New Insights into the Role of Ferritin in Iron Homeostasis and Neurodegenerative Diseases
Zhang, N., Yu, X., Xie, J., & Xu, H. (2021) · Molecular Neurobiology · doi:10.1007/s12035-020-02277-7 · Cited by 218 · see citing works
Proximal tubule H-ferritin mediates iron trafficking in acute kidney injury
Zarjou, A., Bolisetty, S., Joseph, R., Traylor, A., Apostolov, E. O., Arosio, P., Balla, J., Verlander, J. W., Darshan, D., Kühn, L. C., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67867 · Cited by 210 · see citing works
Iron Regulation: Macrophages in Control
Sukhbaatar, N., & Weichhart, T. (2018) · Pharmaceuticals · doi:10.3390/ph11040137 · Cited by 201 · see citing works
Iron Balance and the Role of Hepcidin in Chronic Kidney Disease
Ganz, T., & Nemeth, E. (2016) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2016.02.001 · Cited by 191 · see citing works
Mejías, R., Pérez-Yagüe, S., Gutiérrez, L., Cabrera, L. I., Spada, R., Acedo, P., Serna, C. J., Lázaro, F. J., Villanueva, Á., Morales, M. P., et al. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.01.008 · Cited by 187 · see citing works
Hemochromatosis classification: update and recommendations by the BIOIRON Society
Girelli, D., Busti, F., Brissot, P., Cabantchik, I. Z., Muckenthaler, M. U., & Porto, G. (2021) · Blood · doi:10.1182/blood.2021011338 · Cited by 186 · see citing works
“Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels
Nairz, M., Theurl, I., Swirski, F. K., & Weiss, G. (2017) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-017-1944-8 · Cited by 178 · see citing works
Physiology and pathophysiology of iron in hemoglobin-associated diseases
Coates, T. D. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.03.039 · Cited by 181 · see citing works
Regulation of tissue iron homeostasis: the macrophage “ferrostat”
Winn, N. C., Volk, K. M., & Hasty, A. H. (2020) · JCI Insight · doi:10.1172/jci.insight.132964 · Cited by 177 · see citing works
Zhao, T., Guo, X., & Sun, Y. (2021) · Aging and Disease · doi:10.14336/ad.2020.0912 · Cited by 176 · see citing works
Ineffective erythropoiesis and regulation of iron status in iron loading anaemias
Camaschella, C., & Nai, A. (2016) · British Journal of Haematology · doi:10.1111/bjh.13820 · Cited by 172 · see citing works
Torti, S. V., & Torti, F. M. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-2017 · Cited by 176 · see citing works
Iron metabolism in the pathogenesis of iron-induced kidney injury
Martines, A.-C. M. F., Masereeuw, R., Tjalsma, H., Hoenderop, J. G. J., Wetzels, J. F. M., & Swinkels, D. W. (2013) · Nature Reviews Nephrology · doi:10.1038/nrneph.2013.98 · Cited by 169 · see citing works
Ferritin: An Inflammatory Player Keeping Iron at the Core of Pathogen-Host Interactions
Moreira, A. C., Mesquita, G., & Gomes, M. S. (2020) · Microorganisms · doi:10.3390/microorganisms8040589 · Cited by 166 · see citing works
Nairz, M., Theurl, I., Wolf, D., & Weiss, G. (2016) · Wiener Medizinische Wochenschrift · doi:10.1007/s10354-016-0505-7 · Cited by 152 · see citing works
Zoref‐Lorenz, A., Murakami, J., Hofstetter, L., Iyer, S. P., Alotaibi, A. S., Mohamed, S., Miller, P. G., Guber, E., Weinstein, S., Yacobovich, J., et al. (2021) · Blood · doi:10.1182/blood.2021012764 · Cited by 160 · see citing works
Torti, S. V., & Torti, F. M. (2020) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2020.100860 · Cited by 153 · see citing works
Alkhateeb, A. A., Han, B., & Connor, J. R. (2013) · Breast Cancer Research and Treatment · doi:10.1007/s10549-012-2405-x · Cited by 155 · see citing works
The role of iron in host–microbiota crosstalk and its effects on systemic glucose metabolism
Mayneris‐Perxachs, J., Moreno‐Navarrete, J. M., & Fernández‐Real, J. M. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00721-3 · Cited by 158 · see citing works
Iron in the Tumor Microenvironment-Connecting the Dots
Pfeifhofer-Obermair, C., Tymoszuk, P., Petzer, V., Weiss, G., & Nairz, M. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00549 · Cited by 151 · see citing works
Macrophage activation syndrome: early diagnosis is key
Lerkvaleekul, B., & Vilaiyuk, S. (2018) · Open Access Rheumatology Research and Reviews · doi:10.2147/oarrr.s151013 · Cited by 151 · see citing works
Yanatori, I., Richardson, D. R., Dhekne, H. S., Toyokuni, S., & Kishi, F. (2021) · Blood · doi:10.1182/blood.2021010995 · Cited by 148 · see citing works
Iron Homeostasis Disorder and Alzheimer’s Disease
Peng, Y., Chang, X., & Lang, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212442 · Cited by 143 · see citing works
NCOA4 drives ferritin phase separation to facilitate macroferritinophagy and microferritinophagy
Ohshima, T., Yamamoto, H., Sakamaki, Y., Saito, C., & Mizushima, N. (2022) · The Journal of Cell Biology · doi:10.1083/jcb.202203102 · Cited by 143 · see citing works
Iron and Intracerebral Hemorrhage: From Mechanism to Translation
Xiong, X.-Y., Wang, J., Qian, Z., & Yang, Q. (2013) · Translational Stroke Research · doi:10.1007/s12975-013-0317-7 · Cited by 142 · see citing works
Isotopic evidence of unaccounted for Fe and Cu erythropoietic pathways
Albarède, F., Télouk, P., Lamboux, A., Jaouen, K., & Balter, V. (2011) · Metallomics · doi:10.1039/c1mt00025j · Cited by 132 · see citing works
Diamanti, A. P., Rosado, M. M., Pioli, C., Sesti, G., & Laganà, B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093330 · Cited by 129 · see citing works
Malignancy-associated haemophagocytic lymphohistiocytosis
Setiadi, A., Zoref-Lorenz, A., Lee, C. Y., Jordan, M. B., & Chen, L. Y. C. (2022) · The Lancet Haematology · doi:10.1016/s2352-3026(21)00366-5 · Cited by 128 · see citing works
Iron metabolism and related genetic diseases: A cleared land, keeping mysteries
Brissot, P., & Loréal, O. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.11.009 · Cited by 126 · see citing works
Hyperferritinemia—A Clinical Overview
Sandnes, M., Ulvik, R. J., Vorland, M., & Reikvam, H. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10092008 · Cited by 139 · see citing works
Iron and innate antimicrobial immunity-depriving the pathogen, defending the host
Nairz, M., Dichtl, S., Schroll, A., Haschka, D., Tymoszuk, P., Theurl, I., & Weiss, G. (2018) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2018.03.007 · Cited by 123 · see citing works
Urrutia, P. J., Bórquez, D. A., & Núñez, M. (2021) · Antioxidants · doi:10.3390/antiox10010061 · Cited by 121 · see citing works
van Raaij, S. E. G., van Swelm, R. P. L., Bouman, K., Cliteur, M. P., van den Heuvel, M. C., Pertijs, J. C. L. M., Patel, D., Bass, P., van Goor, H., Unwin, R. J., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-27107-8 · Cited by 120 · see citing works
Emerging and Dynamic Biomedical Uses of Ferritin
Chiou, B., & Connor, J. R. (2018) · Pharmaceuticals · doi:10.3390/ph11040124 · Cited by 119 · see citing works
Hepcidin regulates ferroportin expression and intracellular iron homeostasis of erythroblasts
Zhang, D.-L., Senecal, T., Ghosh, M. C., Ollivierre-Wilson, H., Tu, T., & Rouault, T. A. (2011) · Blood · doi:10.1182/blood-2011-01-330241 · Cited by 113 · see citing works
Kappert, K., Jahić, A., & Tauber, R. (2020) · Biomarkers · doi:10.1080/1354750x.2020.1797880 · Cited by 117 · see citing works
High Fat Diet Induces Liver Steatosis and Early Dysregulation of Iron Metabolism in Rats
Meli, R., Raso, G. M., Irace, C., Simeoli, R., Pascale, A. D., Paciello, O., Pagano, T. B., Calignano, A., Colonna, A., & Santamaria, R. (2013) · PLoS ONE · doi:10.1371/journal.pone.0066570 · Cited by 112 · see citing works
Bertoli, S., Paubelle, É., Bérard, E., Saland, E., Thomas, X., Tavitian, S., Larcher, M., Vergez, F., Delabesse, É., Sarry, A., et al. (2018) · European Journal Of Haematology · doi:10.1111/ejh.13183 · Cited by 110 · see citing works
Zhang, D.-L., Ghosh, M. C., Ollivierre, H., Li, Y., & Rouault, T. A. (2018) · Blood · doi:10.1182/blood-2018-04-842997 · Cited by 107 · see citing works
Iron Regulatory Proteins Mediate Host Resistance to Salmonella Infection
Nairz, M., Ferring-Appel, D., Casarrubea, D., Sonnweber, T., Viatte, L., Schroll, A., Haschka, D., Fang, F. C., Hentze, M. W., Weiss, G., et al. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.06.017 · Cited by 103 · see citing works
Cellular and mitochondrial iron homeostasis in vertebrates
Chen, C., & Paw, B. H. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.01.003 · Cited by 106 · see citing works
Ferritin Light Chain Confers Protection Against Sepsis-Induced Inflammation and Organ Injury
Zarjou, A., Black, L. M., McCullough, K., Hull, T. D., Esman, S. K., Boddu, R., Varambally, S., Chandrashekar, D. S., Feng, W., Arosio, P., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00131 · Cited by 106 · see citing works
Inflammation associated anemia and ferritin as disease markers in SLE
Vanarsa, K., Ye, Y., Han, J., Xie, C., Mohan, C., & Wu, T. (2012) · Arthritis Research & Therapy · doi:10.1186/ar4012 · Cited by 101 · see citing works
Macrophages: central regulators of iron balance
Gammella, E., Buratti, P., Cairo, G., & Recalcati, S. (2014) · Metallomics · doi:10.1039/c4mt00104d · Cited by 95 · see citing works
Iron transport in the kidney: implications for physiology and cadmium nephrotoxicity
Thévenod, F., & Wolff, N. A. (2015) · Metallomics · doi:10.1039/c5mt00215j · Cited by 98 · see citing works
Ruscitti, P., Berardicurti, O., Benedetto, P. D., Cipriani, P., Iagnocco, A., Shoenfeld, Y., & Giacomelli, R. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01130 · Cited by 98 · see citing works
Traglia, M., Girelli, D., Biino, G., Campostrini, N., Corbella, M., Sala, C., Masciullo, C., Viganò, F., Buetti, I., Pistis, G., et al. (2011) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2011-100061 · Cited by 97 · see citing works
Iron metabolism: current facts and future decisions
Tandara, L., & Salamunić, I. (2012) · Biochemia Medica · doi:10.11613/bm.2012.034 · Cited by 96 · see citing works
Iron Uptake Mediated by Binding of H-Ferritin to the TIM-2 Receptor in Mouse Cells
Han, J., Seaman, W. E., Di, X., Wang, W., Willingham, M. C., Torti, F. M., & Torti, S. V. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023800 · Cited by 93 · see citing works
Hepatic iron is the major determinant of serum ferritin in NAFLD patients
Ryan, J. D., Armitage, A. E., Cobbold, J., Banerjee, R., Borsani, O., Dongiovanni, P., Neubauer, S., Morovat, R., Wang, L. M., Pasricha, S., et al. (2017) · Liver International · doi:10.1111/liv.13513 · Cited by 93 · see citing works
Endoplasmic reticulum anchored heme-oxygenase 1 faces the cytosol
Gottlieb, Y., Truman-Rosentsvit, M., Cohen, L. A., Leichtmann‐Bardoogo, Y., & Meyron‐Holtz, E. G. (2012) · Haematologica · doi:10.3324/haematol.2012.063651 · Cited by 86 · see citing works
Iron and the heart: A paradigm shift from systemic to cardiomyocyte abnormalities
Paterek, A., Mackiewicz, U., & Ma̧czewski, M. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28820 · Cited by 85 · see citing works
Ruscitti, P., Cipriani, P., Ciccia, F., Masedu, F., Liakouli, V., Carubbi, F., Berardicurti, O., Guggino, G., Benedetto, P. D., Bartolomeo, S. D., et al. (2016) · Autoimmunity Reviews · doi:10.1016/j.autrev.2016.09.016 · Cited by 85 · see citing works
sCD163 in AOSD: a biomarker for macrophage activation related to hyperferritinemia
Colafrancesco, S., Priori, R., Alessandri, C., Astorri, E., Perricone, C., Blank, M., Agmon‐Levin, N., Shoenfeld, Y., & Valesini, G. (2014) · Immunologic Research · doi:10.1007/s12026-014-8563-7 · Cited by 83 · see citing works
Boyce, M. J., Warrington, S., Cortezi, B., Zöllner, S. K., Vauléon, S., Swinkels, D. W., Summo, L., Schwoebel, F., & Riecke, K. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13433 · Cited by 81 · see citing works
Iron Load Toxicity in Medicine: From Molecular and Cellular Aspects to Clinical Implications
Kontoghiorghes, G. J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241612928 · Cited by 79 · see citing works
A possible role for secreted ferritin in tissue iron distribution
Meyron‐Holtz, E. G., Moshe-Belizowski, S., & Cohen, L. A. (2011) · Journal of Neural Transmission · doi:10.1007/s00702-011-0582-0 · Cited by 78 · see citing works
Gowda, P., Patrick, S., Joshi, S. D., Kumawat, R. K., & Sen, E. (2021) · Cytokine · doi:10.1016/j.cyto.2021.155496 · Cited by 79 · see citing works
Leichtmann‐Bardoogo, Y., Cohen, L. A., Weiss, A., Marohn, B., Schubert, S., Meinhardt, A., & Meyron‐Holtz, E. G. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00007.2012 · Cited by 77 · see citing works
Time-course assessment of the aggregation and metabolization of magnetic nanoparticles
Rojas, J. M., Gavilán, H., del Dedo, V., Lorente-Sorolla, E., Sanz-Ortega, L., da Silva, G. B., Costo, R., Pérez-Yagüe, S., Talelli, M., Marciello, M., et al. (2017) · Acta Biomaterialia · doi:10.1016/j.actbio.2017.05.047 · Cited by 76 · see citing works
Macrophages and Iron: A Special Relationship
Recalcati, S., & Cairo, G. (2021) · Biomedicines · doi:10.3390/biomedicines9111585 · Cited by 74 · see citing works
Laskar, A., Ghosh, M., Khattak, S. I., Li, W., & Yuan, X. (2012) · Nanomedicine · doi:10.2217/nnm.11.148 · Cited by 75 · see citing works
Hepcidin and ferritin blood level as noninvasive tools for predicting breast cancer
Orlandi, R., De Bortoli, M., Ciniselli, C. M., Vaghi, E., Caccia, D., Garrisi, V., Pizzamiglio, S., Veneroni, S., Bonini, C., Agresti, R., et al. (2014) · Annals of Oncology · doi:10.1093/annonc/mdt490 · Cited by 74 · see citing works
- Authors
- Cohen, L. A., Gutierrez, L., Weiss, A., Leichtmann-Bardoogo, Y., Zhang, D.-L., Crooks, D. R., Sougrat, R., Morgenstern, A., Galy, B., Hentze, M. W., Lazaro, F. J., Rouault, T. A., & Meyron-Holtz, E. G.
- Affiliations
- Technion – Israel Institute of Technology (IL)
- Departamento de Ciencia y Tecnología de Materiales y Fluidos, Universidad de Zaragoza, Zaragoza, Spain;
- Laboratory for Molecular Nutrition, Faculty of Biotechnology and Food Engineering, Technion, Technion City, Haifa, Israel;
- Molecular Medicine Program and
- National Institutes of Health (US)
- European Molecular Biology Laboratory (DE)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2010-09-02
- Volume
- 116
- Issue
- 9
- Pages
- 1574-1584
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2153170511
- Cited by
- 452
- References
- 53
- Citations by year
- 2026: 8 · 2025: 34 · 2024: 33 · 2023: 30 · 2022: 43 · 2021: 45 · 2020: 35 · 2019: 34 · 2018: 31 · 2017: 24 · 2016: 23 · 2015: 33 · 2014: 18 · 2013: 24 · 2012: 17
- FWCI
- 11.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- serum ferritin, macrophages, lysosomal secretion, L subunit, H subunit, C-terminal truncation, glycosylation, proximal tubular epithelial cells, splenic macrophages, iron stores, mice
- MeSH terms
- Amino Acid Sequence, Animals, Enzyme-Linked Immunosorbent Assay, Ferritins, Glycosylation, Iron, Lysosomes, Macrophages, Male, Mice, Inbred C57BL, Molecular Sequence Data, Sequence Homology, Amino Acid, Iron Overload, Protein Subunits, Mice, Secretory Pathway
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