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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.
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“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]
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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
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