The DOI matches its Crossref record; 51 of the 53 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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
In the citing paper
“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
Citations
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
Blott, E. J., & Griffiths, G. M. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm732 · Cited by 703
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
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
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
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
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 366
Jacobs, A., & Worwood, M. (1975) · New England Journal of Medicine · doi:10.1056/nejm197505012921805 · Cited by 353
Nichol, H., Law, J. H., & Winzerling, J. J. (2002) · Annual Review of Entomology · doi:10.1146/annurev.ento.47.091201.145237 · Cited by 282
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
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
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 210
Quintana, C., COWLEY, J. M., & Marhic, C. (2004) · Journal of Structural Biology · doi:10.1016/j.jsb.2004.03.001 · Cited by 189
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
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
Jiang, Y., Oliver, P. L., Davies, K. E., & Platt, N. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m507599200 · Cited by 156
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
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 132
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
Mizuno, M., & Singer, S. J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.12.5732 · Cited by 121
Zhang, D., Meyron‐Holtz, E. G., & Rouault, T. A. (2007) · Journal of the American Society of Nephrology · doi:10.1681/asn.2006080908 · Cited by 110
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
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
Worwood, M., & Cook, J. D. (1979) · CRC Critical Reviews in Clinical Laboratory Sciences · doi:10.3109/10408367909147133 · Cited by 104
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
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 87
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 83
Smith, C. P., & Thévenod, F. (2008) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2008.10.010 · Cited by 80
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
Aguilar‐Martinez, P., Schved, J., & Brissot, P. (2005) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2005.40998.x · Cited by 73
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
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
Self-citationIron and ferritin in inflammation and cancer.
Torti, S. V., & Torti, F. M. (1994) · PubMed · Cited by 53
Ferring–Appel, D., Hentze, M. W., & Galy, B. (2008) · Blood · doi:10.1182/blood-2008-05-155093 · Cited by 53
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
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
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
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
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
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
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
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
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
[New observations on the erythroblast islet and rhopheocytosis of ferritin].
BESSIS, M. C., & Breton-Gorius, J. (2000) · PubMed · Cited by 14
The diagnostic value of serum ferritin determinations for assessing iron status.
Worwood, M. (1987) · PubMed · Cited by 13
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
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
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
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
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
[The erythroblastic islet and the rhopheocytosis of ferritin in inflammation].
BESSIS, M. C., & Breton-Gorius, J. (1998) · PubMed · Cited by 5
Cited by
Sorted by citations
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
Weiss, G., Ganz, T., & Goodnough, L. T. (2019) · Blood · doi:10.1182/blood-2018-06-856500 · Cited by 1,219
Ganz, T. (2013) · Physiological Reviews · doi:10.1152/physrev.00008.2013 · Cited by 1,122
Regulation of cellular iron metabolism
Wang, J., & Pantopoulos, K. (2011) · Biochemical Journal · doi:10.1042/bj20101825 · Cited by 986
Transferrin and transferrin receptors update
Kawabata, H. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.06.037 · Cited by 719
Metadata
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
