The DOI matches its Crossref record; 150 of the 152 references it cites were found in a registry or an index.
Macrophages and Iron Metabolism
Open accessAbstract
Iron is a transition metal that due to its inherent ability to exchange electrons with a variety of molecules is essential to support life. In mammals, iron exists mostly in the form of heme, enclosed within an organic protoporphyrin ring and functioning primarily as a prosthetic group in proteins. Paradoxically, free iron also has the potential to become cytotoxic when electron exchange with oxygen is unrestricted and catalyzes the production of reactive oxygen species. These biological properties demand that iron metabolism is tightly regulated such that iron is available for core biological functions while preventing its cytotoxic effects. Macrophages play a central role in establishing this delicate balance. Here, we review the impact of macrophages on heme-iron metabolism and, reciprocally, how heme-iron modulates macrophage function.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Macrophage plays a central role in iron metabolism, including heme-iron turnover in senescent red blood cells, hepcidin regulation and lipocalin system [68].”
From Asbestos conceives Fe(II)-dependent mutagenic stromal milieu through ceaseless macrophage ferroptosis and β-catenin induction in mesothelium (2020) · cites this paper as [68]
Experimental — accuracy not yet measuredIn the citing paper
“Second, the degradation of Bach1 induces expression of the transcription factor (an E26 transformation-specific transcription factor of the Spi subfamily) SpiC independently of Nrf2 [116, 211].”
From “Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels (2017) · cites this paper as [211]
In the citing paper
“This is circumvented by the recycling of the Fe contained in the heme groups of Hb inside RBC (14–16), achieved largely via the continuous engulfment and digestion of senescent or damaged RBC by erythrophagocytic macrophages (EM) in the red pulp of the spleen (15) (Figure 1).”
From Innate Nutritional Immunity (2018) · cites this paper as [15]
In the citing paper
“This process allows for the Fe contained in the heme groups of Hb to be extracted and directed into the bone marrow to support erythropoiesis, where Fe is inserted in the last step of heme biosynthesis and incorporated into nascent Hb (15) (Figure 1).”
From Innate Nutritional Immunity (2018) · cites this paper as [15]
In the citing paper
“In addition, pathogen sensing via PRRs promotes resistance mechanisms in innate immune cells, which withhold heme-Fe from pathogens (15) (Figure 3).”
From Innate Nutritional Immunity (2018) · cites this paper as [15]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Dixon, S. J., Lemberg, K. M., Lamprecht, M. R., Skouta, R., Zaitsev, E. M., Gleason, C. E., Patel, D. N., Bauer, A. J., Cantley, A. M., Yang, W. S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.042 · Cited by 18,691
Janeway, C. A., & Medzhitov, R. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.083001.084359 · Cited by 8,394
The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
Bedard, K., & Krause, K.-H. (2007) · Physiological Reviews · doi:10.1152/physrev.00044.2005 · Cited by 6,989
Origin and physiological roles of inflammation
Medzhitov, R. (2008) · Nature · doi:10.1038/nature07201 · Cited by 6,618
Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly
Beckman, J. S., & Koppenol, W. H. (1996) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1996.271.5.c1424 · Cited by 5,513
Macrophage biology in development, homeostasis and disease
Wynn, T. A., Chawla, A., & Pollard, J. W. (2013) · Nature · doi:10.1038/nature12034 · Cited by 4,684 · cited 2×
“However, intracellular iron also downregulates NOS2 transcription in response to IFN-g (Weiss et al., 1992) via a mechanism involving STAT inhibition (Xie et al., 1994).”
BackgroundHypoxia-inducible factors in physiology and medicine
Semenza, G. L. (2012) · Cell · doi:10.1016/j.cell.2012.01.021 · Cited by 3,645
Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J. D., & Yamamoto, M. (1999) · Genes & Development · doi:10.1101/gad.13.1.76 · Cited by 3,634
Cell Survival Responses to Environmental Stresses Via the Keap1-Nrf2-ARE Pathway
Kensler, T. W., Wakabayashi, N., & Biswal, S. (2007) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.46.120604.141046 · Cited by 3,630
Targeting the KEAP1-NRF2 system to prevent kidney disease progression
Nezu, M., Suzuki, N., & Yamamoto, M. (2017) · American Journal of Nephrology · doi:10.1159/000475890 · Cited by 3,447
Cited by
Sorted by citations
Cross-tissue immune cell analysis reveals tissue-specific features in humans
Conde, C. D., Xu, C., Jarvis, L. B., Rainbow, D. B., Wells, S. B., Gomes, T., Howlett, S. K., Suchánek, O., Polański, K., King, H. W., et al. (2022) · Science · doi:10.1126/science.abl5197 · Cited by 1,246
Lipid Peroxidation and Iron Metabolism: Two Corner Stones in the Homeostasis Control of Ferroptosis
Rochette, L., Dogon, G., Rigal, E., Zeller, M., Cottin, Y., & Vergely, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010449 · Cited by 966
The Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis
Hirayama, D., Iida, T., & Nakase, H. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms19010092 · Cited by 927
Phagocytosis: An Immunobiologic Process
Gordon, S. (2016) · Immunity · doi:10.1016/j.immuni.2016.02.026 · Cited by 902
Tissue macrophages: heterogeneity and functions
Gordon, S., & Plüddemann, A. (2017) · BMC Biology · doi:10.1186/s12915-017-0392-4 · Cited by 628
Metadata
- Authors
- Soares, M. P., & Hamza, I.
- Affiliations
- Instituto Gulbenkian de Ciência (PT)
- University of Maryland, College Park (US)
- Corresponding author
- Soares, Miguel P.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 44
- Issue
- 3
- Pages
- 492-504
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC4794998
- OpenAlex
- W2298261633
- Cited by
- 401
- References
- 152
- Citations by year
- 2026: 39 · 2025: 47 · 2024: 38 · 2023: 44 · 2022: 50 · 2021: 53 · 2020: 42 · 2019: 31 · 2018: 24 · 2017: 28 · 2016: 4
- FWCI
- 4.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI067979, R41AI113998)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK085035, R01DK074797)
- National Institute of Environmental Health Sciences (R21ES025661, R33ES025661)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Keywords
- macrophages, iron metabolism, heme iron, reactive oxygen species, iron regulation, macrophage function
- MeSH terms
- Animals, Heme, Humans, Iron, Macrophages, Protoporphyrins, Reactive Oxygen Species
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
