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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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“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
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Sub-cellular In-situ Characterization of Ferritin(iron) in a Rodent Model of Spinal Cord Injury
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“Serum ferritin is also relatively iron poor and its source was not completely understood until it was revealed by Cohen and colleagues that macrophages are the primary source of serum ferritin [11].”
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“22,23 Pharmacokinetic studies have reported a rapid rise in plasma non-transferrin-bound iron (NTBI) following treatment with IV iron, indicating that some iron is released from the carbohydrate complex directly into the circulation.”
BackgroundHilton, R. J., Andros, N. D., & Watt, R. K. (2011) · BioMetals · doi:10.1007/s10534-011-9500-z · Cited by 28
“Iron may be acquired by ferritin during the secretion process as it passes through the endoplasmic reticulum and Golgi apparatus or serum ferritin may acquire iron once it enters the bloodstream (De Domenico et al. 2011; Cohen et al. 2010).”
BackgroundIron Therapy Challenges for the Treatment of Nondialysis CKD Patients
Locatelli, F., Mazzaferro, S., & Yee, J. (2016) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.00080116 · Cited by 27
“Interestingly, serum ferritin is derived from the same gene sequence as intracellular ferritin; however, serum ferritin is iron poor, because it consists predominantly of L-chain subunits, and there may be a combination of ferritin and apoferritin (not combined with iron) (15).”
BackgroundLeitch, H. A., Buckstein, R. J., Zhu, N. Y., Nevill, T. J., Yee, K. W. L., Leber, B. F., Keating, M., St‐Hilaire, È., Kumar, R., Delage, R., et al. (2018) · Leukemia Research · doi:10.1016/j.leukres.2018.09.005 · Cited by 27
Translational repression of HIF2α expression in mice with Chuvash polycythemia reverses polycythemia
Ghosh, M. C., Zhang, D., Ollivierre, H., Eckhaus, M., & Rouault, T. A. (2018) · Journal of Clinical Investigation · doi:10.1172/jci97684 · Cited by 27
Weiss, A., Spektor, L., Cohen, L. A., Lifshitz, L., Magid-Gold, I., Zhang, D., Truman-Rosentsvit, M., Leichtmann‐Bardoogo, Y., Nyska, A., Addadi, Y., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0204471 · Cited by 26
Use of C-Reactive Protein and Ferritin Biomarkers in Daily Pediatric Practice
Taylor, M. D., Allada, V., Moritz, M. L., Nowalk, A. J., Sindhi, R. K., Aneja, R. K., Torok, K. S., Morowitz, M. J., Michaels, M. G., & Carcillo, J. A. (2020) · Pediatrics in Review · doi:10.1542/pir.2018-0101 · Cited by 25
Iron homeostasis and infIammatory biomarker analysis in patients with type 1 Gaucher disease
Medrano-Engay, B., Irún, P., Gervas‐Arruga, J., Andrade‐Campos, M., Andreu, V., Alfonso, P., Pocovı́, M., & Giraldo, P. (2014) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2014.07.007 · Cited by 25
Tajima, S., Ikeda, Y., Enomoto, H., Imao, M., Horinouchi, Y., Izawa‐Ishizawa, Y., Kihira, Y., Miyamoto, L., Ishizawa, K., Tsuchiya, K., et al. (2014) · European Journal of Nutrition · doi:10.1007/s00394-014-0749-1 · Cited by 25
“and serum ferritin may be derived from macrophages [25].”
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“1 3,53,55 In healthy adults, serum ferritin levels are generally maintained at levels of ≈ 20–300 μ g/L in men and ≈ 20–200 μ g/L in women.”
BackgroundRETRACTED: Decoupling Ferritin Synthesis from Free Cytosolic Iron Results in Ferritin Secretion
Domenico, I. D., Vaughn, M. B., Paradkar, P. N., Lo, E., Ward, D. M., & Kaplan, J. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2010.12.003 · Cited by 24
“A recent study suggested that serum ferritin was primarily derived from the release of ferritin from macrophage lysosomes (Cohen et al., 2010).”
InfluentialRetractedGutiérrez, L., Morales, M. P., & Lázaro, F. J. (2014) · Physical Chemistry Chemical Physics · doi:10.1039/c3cp54763a · Cited by 24
Iron uptake at the blood-brain barrier is influenced by sex and genotype
Wade, Q. W., Chiou, B., & Connor, J. R. (2019) · Advances in pharmacology · doi:10.1016/bs.apha.2019.02.005 · Cited by 24
Fernández‐Afonso, Y., Asín, L., Beola, L., Moros, M., de la Fuente, J. M., Fratila, R. M., Grazú, V., & Gutiérrez, L. (2022) · ACS Applied Bio Materials · doi:10.1021/acsabm.1c01200 · Cited by 24
Gutiérrez, L., Spasić, M. V., Muckenthaler, M. U., & Lázaro, F. J. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.03.008 · Cited by 24
Targeting secretory autophagy in solid cancers: mechanisms, immune regulation and clinical insights
Li, X., & Zhao, H. (2025) · Experimental Hematology and Oncology · doi:10.1186/s40164-025-00603-0 · Cited by 25
“Serum ferritin, another unconventional secreted protein associated with inflammation, has also been shown to be secreted through unconventional pathways [62].”
Redox mechanism of glycerophospholipids and relevant targeted therapy in ferroptosis
Chang, S., Zhang, M., Liu, C., Li, M., Lou, Y., & Tan, H. (2025) · Cell Death Discovery · doi:10.1038/s41420-025-02654-y · Cited by 32
Serum ferritin is a good indicator for predicting the efficacy of adult HLH induction therapy
Hua, Z., He, L., Zhang, R., Liu, M., Wang, Z., & Wang, Y. (2022) · Annals of Medicine · doi:10.1080/07853890.2022.2027513 · Cited by 23
“which is mainly found in macrophages [4].”
BackgroundToxicity and biodegradation of zinc ferrite nanoparticles in Xenopus laevis
Rivero, M., Marin-Barba, M., Gutiérrez, L., Lozano-Velasco, E., Wheeler, G. N., Sánchez‐Marcos, J., Muñoz‐Bonilla, A., Morris, C. J., & Ruiz, A. (2019) · Journal of Nanoparticle Research · doi:10.1007/s11051-019-4631-1 · Cited by 22
“The location in temperature of this signal agrees with previous measurements of ferritin, the iron storage protein, whose biomineralized core always presents a similar magnetic behaviour (independently of the animal species) when measured in the same conditions (Gutierrez et al. 2006, 2013; Cohen et al. 2010).”
ResultRaha, A. A., Ghaffari, S. D., Henderson, J. W., Chakraborty, S., Allinson, K. S. J., Friedland, R. P., Holland, A. J., Zaman, S. H., Mukaetova-Ladinska, E. B., & Raha‐Chowdhury, R. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.653591 · Cited by 21
“The hyperinflammatory response induced by SARS-CoV-2 through peripheral macrophages is a major cause of disease severity (Cohen et al., 2010).”
BackgroundGreene, C., Attwood, K. M., Sharma, N. J., Balderman, B., Deng, R., Muhitch, J. B., Smith, G. J., Gross, K. W., Xu, B., & KAUFFMAN, E. C. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.923043 · Cited by 23
Piperno, A., Pelucchi, S., & Mariani, R. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032560 · Cited by 22
“In mice, serum ferritin consists mainly of L-subunits, contains few H-subunits, and small amounts of iron as in humans, whereas glycosylated ferritin is undetectable and L-subunits are often truncated at the C-terminus (S-ferritin), resulting in a characteristic 17-kD band previously observed in lysosomal ferritin [27…”
BackgroundInfluentialTseng, W. K., Chieh, J.-J., Yang, Y.-F., Chiang, C., Chen, Y., Yang, S. Y., Horng, H. E., Yang, H.-C., & Wu, C.-C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048510 · Cited by 22
“Except for magnetic resonance imaging (MRI), alternating current (AC) magnetic susceptometry [17–18] is currently the most sensitive method available for measuring variations in magnetism when preformed using a superconducting quantum interference device (SQUID) magnetometer.”
BackgroundKidder, K., Bian, Z., Shi, L., & Liu, Y. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.2000652 · Cited by 23
“sHLH symptoms associated with macrophage activation, such as hypercytokinemia, hypertriglyceridemia and hyperferritinemia, were less severe in CpGtreated CD47−/− mice than in SIRPα−/− mice (21, 24, 25).”
BackgroundFerritin Assembly in Enterocytes of Drosophila melanogaster
Rosas‐Arellano, A., Vásquez-Procopio, J., Gambis, A., Blowes, L. M., Steller, H., Mollereau, B., & Missirlis, F. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17020027 · Cited by 21
“Given that ferritins isolated from different mammalian tissues show differences in the ratios of the two types of their subunits, the regulation of ferritin assembly in vivo requires further investigation [47–53].”
Zoref‐Lorenz, A., Witzig, T. E., Cerhan, J. R., & Jordan, M. B. (2024) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428194.2024.2436037 · Cited by 20
Kawabata, H., Tamura, T., Tamai, S., Fujibayashi, A., Sugimura, M., Study Group, Hayakawa, J., Oku, H., Ota, Y., Nishiguchi, S., et al. (2022) · International Journal of Hematology · doi:10.1007/s12185-022-03401-0 · Cited by 20
“Because serum ferritin is derived primarily from macrophages [20], its level essentially reflects the amount of stored iron in the reticuloendothelial macrophages.”
BackgroundGong, L., Yu, Q., Wang, H., Xu, C., Dou, Y., Mao, B., & Zhao, Y. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/3938940 · Cited by 19
“However, recent evidence revealed two potential mechanisms underlying the secretion of ferritin including exosome-mediated and autophagy-mediated pathways [22, 23].”
Identifying critically ill patients at risk of death from coronavirus disease
Guo, W., Ran, L.-Y., Zhu, J., Ge, Q., Du, Z., Wang, F., Gao, W., & Wang, T. (2020) · World Journal of Emergency Medicine · doi:10.5847/wjem.j.1920-8642.2021.01.003 · Cited by 18
Host and microbiota derived extracellular vesicles: Crucial players in iron homeostasis
Daou, Y., Falabrègue, M., Pourzand, C., Peyssonnaux, C., & Edeas, M. A. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.985141 · Cited by 19
“showed that ferritin is secreted primarily by macrophages through lysosomal pathway, by secretory lysosomes (55).”
BackgroundYin, D., Kulhalli, V., & Walker, A. P. (2013) · Hepatology · doi:10.1002/hep.26681 · Cited by 18
“Serum ferritin is thought to be mainly secreted by macrophages, although hepatocytes and other cells may also contribute.(2) In HHCS, L-ferritin synthesis is uncoupled from cellular iron stores so that hyperferritinemia indicates unregulated L-ferritin synthesis, not iron overload.”
BackgroundThe hyperferritinemic syndromes and CD163: a marker of macrophage activation.
Colafrancesco, S., Priori, R., Alessandri, C., Astorri, E., Perricone, C., Blank, M., Agmon‐Levin, N., Shoenfeld, Y., & Valesini, G. (2014) · PubMed · Cited by 18
Extreme hyperferritinaemia, soluble interleukin‐2 receptor, and haemophagocytic lymphohistiocytosis
Chen, L. Y. C., Hayden, A. R., & Mattman, A. (2018) · British Journal of Haematology · doi:10.1111/bjh.15579 · Cited by 18
“The main source of serum ferritin is secretion by macrophages via non-classical lysosomal path- ways (Cohen et al, 2010); thus it is not surprising that fer- ritin is markedly elevated in haemophagocytic syndromes.”
BackgroundYan, L., Chen, S., Hou, C., Lin, J., Xiong, W., Shen, Y., & Zhou, T. (2022) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2022.155642 · Cited by 17
Chen, Z.-T., Pan, C.-Z., Ruan, X.-L., Lei, L.-P., Lin, S.-M., Wang, Y., & Zhao, Z. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1216905 · Cited by 17
“Notably, since mammalian ferritin lacks signaling peptides that regulate classical Golgi secretion, extracellular secretion of ferritin is mainly achieved through non-classical protein secretion pathways, secretory autophagy (Cohen et al., 2010) and exosome pathway (Truman-Rosentsvit et al., 2018).”
Brands, X., de Vries, F. M. C., Uhel, F., Haak, B. W., Sengers, H. P., Schuurman, A. R., van Engelen, T. S. R., Lutter, R., Cremer, O. L., Bonten, M. J. M., et al. (2021) · Critical Care Medicine · doi:10.1097/ccm.0000000000005072 · Cited by 17
“Macrophages are an important source of serum ferritin, which may account for the association between MAS and very high ferritin levels (15).”
BackgroundNos, F. C., Hernández, G., Ferrer-Cortés, X., Hernández‐Rodríguez, I., Navarro-Almenzar, B., Fuster, J. L., Cortés, M. B., Pérez-Montero, S., Tornador, C., & Sánchez, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115451 · Cited by 18
“Furthermore, serum ferritin is mainly constituted by L-ferritin and is partially glycosylated [9].”
BackgroundSen, S., Bal, S. K., Yadav, S., Mishra, P., Vishnu Vivek, G., Rastogi, R., & Mukhopadhyay, C. K. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102646 · Cited by 17
“Ferrozine assay- Iron content in ferritin in J774 cells and splenocytes were estimated as described earlier (35).”
MethodIron homeostasis in the heart: Molecular mechanisms and pharmacological implications
Zhang, J., Song, Y., Li, Y., Lin, H.-B., & Fang, X. (2022) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2022.11.001 · Cited by 16
Adipose knockout of H-ferritin improves energy metabolism in mice
Lu, B., Guo, S., Zhao, J., Wang, X., & Zhou, B. (2024) · Molecular Metabolism · doi:10.1016/j.molmet.2024.101871 · Cited by 16
Acute Phase Proteins: Ferritin and Ferritin Isoforms
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“In a recent study it was shown that murine serum ferritin is mainly secreted by macrophages through a non-classical secretion process involving secretory lysosomes and not the endoplasmic reticulum (Cohen et al., 2010).”
Why is Iron Deficiency Recognised as an Important Comorbidity in Heart Failure?
Ebner, N., & von Haehling, S. (2019) · Cardiac failure review · doi:10.15420/cfr.2019.9.2 · Cited by 16
“suggested that serum ferritin is not a major pathway of systemic iron transport, but locally secreted ferritin may play such a role in selected tissues.(18) Despite there being some insight, the detailed pathways that enable iron trafficking from the endosome to the mitochondria and to other cellular sites are not wel…”
BackgroundFerritin index is a strong prognostic marker in adult hemophagocytic lymphohistiocytosis
Zhou, J., Zhou, J., Wu, Z., Goyal, H., & Xu, H. (2020) · International Journal of Clinical Practice · doi:10.1111/ijcp.13704 · Cited by 16
Ferritin polarization and iron transport across monolayer epithelial barriers in mammals
Meyron‐Holtz, E. G., Cohen, L. A., Fahoum, L., Haimovich, Y., Lifshitz, L., Magid-Gold, I., Stuemler, T., & Truman-Rosentsvit, M. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00194 · Cited by 16
“Moreover, an uneven ferritin distribution was detected in renal proximal tubule cells where ferritin was co-localized with villin and was enriched near the apical pole of the PCT-cells, a region enriched with lysosomes (Cohen et al., 2010).”
Vigan, M., Stirnemann, J., Caillaud, C., Froissart, R., Boutten, A., Fantin, B., Belmatoug, N., & Mentré, F. (2014) · Orphanet Journal of Rare Diseases · doi:10.1186/1750-1172-9-95 · Cited by 21
Hyperferritinemia as a Diagnostic Marker for Severe Fever with Thrombocytopenia Syndrome
Kim, U. J., Oh, T. H., Kim, B.-S., Kim, S. E., Kang, S., Park, K., Jung, S., & Jang, H. (2017) · Disease Markers · doi:10.1155/2017/6727184 · Cited by 16
“The major source of extreme hyperferritinemia seen in HLH or MAS has been suggested to be activated macrophages in the bone marrow or spleen [22, 23].”
BackgroundImpact of Autophagy and Aging on Iron Load and Ferritin in Drosophila Brain
Jacomin, A., Geraki, K., Brooks, J., Tjhin, V. T., Collingwood, J. F., & Nezis, I. P. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00142 · Cited by 16
“Ferritin is also known to be glycosylated in mammals and insects; notably, secreted ferritin L has been shown to be N-glycosylated in culture hepatocytes (Cragg et al., 1981; Ketola-Pirie, 1990; Ghosh et al., 2004; Cohen et al., 2010).”
BackgroundAn islet-resident macrophage antioxidant program preserves β cell physiology
Grosjean, A., Jalon, A., Leveau, C., Diedisheim, M., Bejarano, D. A., Cuenco, J., Mulder, K., Liu, Z., Guernic, A. L., Island, M., et al. (2025) · Science Immunology · doi:10.1126/sciimmunol.adz5181 · Cited by 19
Goubran, M., Spaner, C., Stukas, S. K., Zoref‐Lorenz, A., Shojania, K., Beckett, M., Li, A., Peterson, E. A., Sekhon, M. S., Grey, R., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-82760-6 · Cited by 16
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Hyperferritinemic Sepsis: An Opportunity for Earlier Diagnosis and Intervention?
Halstead, E. S., Rajasekaran, S., Fitzgerald, J. C., & Weiss, S. L. (2016) · Frontiers in Pediatrics · doi:10.3389/fped.2016.00077 · Cited by 15
“So, what is the reason for the hyperferritinemia during HSV infection and for that matter, HLH/macrophage activation syndrome (MAS)? Ferritin is a key molecule that serves to limit pro-oxidant stress that typifies inflammatory conditions (8), and the major source of serum ferritin is tissue macrophages (9).”
BackgroundNCOA4-Mediated Ferritinophagy: A Vicious Culprit in COVID-19 Pathogenesis?
Jia, F., Liu, H., & Kang, S. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.761793 · Cited by 15
“Although the source of circulating serum ferritin in COVID19 has not yet been determined, macrophages contribute considerably to release ferritin via a non-classical secretory pathway (Cohen et al., 2010).”
BackgroundCOVID-19: High-JAKing of the Inflammatory “Flight” by Ruxolitinib to Avoid the Cytokine Storm
Botta, C., Indrieri, A., Garofalo, E., Biamonte, F., Bruni, A., Pasqua, P., Cesario, F., Costanzo, F. S., Longhini, F., & Mendicino, F. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2020.599502 · Cited by 15
“Indeed, despite most of the serum ferritin derives from tissue injury and, in particular, from hepatic cells death, during “hyperferritinemic syndromes”, ferritin could be even actively released by hepatocytes (53) as well as by macrophages (54).”
BackgroundAlkhateeb, A. A., Zubritsky, L., Kinsman, B. J., Leitzel, K., Campbell‐Baird, C., Ali, S. M., Connor, J. R., & Lipton, A. (2014) · Journal of Gastrointestinal Cancer · doi:10.1007/s12029-013-9564-9 · Cited by 15
“On the other hand, serum ferritin could be produced by macrophages [24, 25], and possibly hepatocytes [38], in response to inflammatory cytokines activating the NF-κB pathway such as TNF-α and IL-1β [39].”
BackgroundChen, M., Juengpanich, S., Hu, J., Topatana, W., Cao, J., Tong, C., Lin, J., & Cai, X. (2020) · World Journal of Gastroenterology · doi:10.3748/wjg.v26.i10.1042 · Cited by 14
Izuka, S., Komai, T., Tsuchida, Y., Tsuchiya, H., Okamura, T., & Fujio, K. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1567833 · Cited by 16
“…cellular origin of ferritin in this condition remains unclear, the positive correlation between an increased percentage of HLA-DR low CD14 + monocytes and both serum ferritin and IL-6 levels (54) suggests that these monocytes, in addition to macrophages, may also be a source offerritin (55).”
Moreira, A. C., Silva, T., Mesquita, G., Gomes, A. C., Bento, C. M., Neves, J. V., Rodrigues, D. F., Rodrigues, P., Almeida, A. A., Santambrogio, P., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010269 · Cited by 15
“Furthermore, this high level of FTH1 in the serum was not observed in Fth1−/− mice, indicating that it has a myeloid origin, in line with previous studies indicating that macrophages are the main source of circulating ferritin [35].”
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“Another explanation is that ferritin secretion occurs from the lysosomal compartment as demonstrated in murine bone marrow-derived macrophages (Cohen et al. 2010).”
BackgroundIntravenous Iron Therapy in Heart Failure: A Different Perspective
Ghafourian, K., Chang, H., & Ardehali, H. (2019) · European Journal of Heart Failure · doi:10.1002/ejhf.1434 · Cited by 14
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“While it remains unclear whether ferritin directly participates in systemic iron traf fi cking, Scara5, TIM-2, and TFR1 receptors have been implicated in its endocytosis in human and mouse cells 11 – 13 .”
Zhao, C., Tang, J., Li, X., Yan, Z., Zhao, L., Lang, W., Yuan, C., & Zhou, C. (2022) · Food & Function · doi:10.1039/d1fo03616e · Cited by 13
Pathogenic Mechanisms in Thalassemia II
Ganz, T., & Nemeth, E. (2023) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2022.12.006 · Cited by 17
Iron and the Reticuloendothelial System
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Recognizing and Managing Secondary Hemophagocytic Lymphohistiocytosis in Adults
Zoref‐Lorenz, A., Rocco, J. M., Schwartz, D. M., & Jordan, M. B. (2025) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2025.02.007 · Cited by 12
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“Extracellular vesicles(EVs)arelikely asignificantpathway forferritinsecretion (Cohen et al. 2010; Truman-Rosentsvit et al. 2018).”
SARS–CoV-2 Mediated Hyperferritinemia and Cardiac Arrest: Preliminary Insights
VasanthiDharmalingam, P., Karuppagounder, V., Watanabe, K., Karmouty‐Quintana, H., Palaniyandi, S. S., Guha, A., & Thandavarayan, R. A. (2021) · Drug Discovery Today · doi:10.1016/j.drudis.2021.01.014 · Cited by 13
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“Moreover, the secretion pathway for ferritin is incompletely understood as some studies suggest that ferritin is secreted through the classical secretion pathway involving endoplasmic reticulum and the Golgi aparatus,(24) while others report that ferritin is secreted through nonclassical secretion pathway involving se…”
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“The H-ferritin subunit expression was not affected in either genotype by any of the iron manipulations (Fig.”
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“More recently, however, secreted ferritin has also been proposed as an alternative route of iron export (18), although mammalian ferritin lacks a signal peptide for conventional ER – Golgi secretion.”
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“When the liver is damaged by viral infection, ferritin is released from the damaged hepatic cells and actively secreted by macrophages during inflammation as well [26].”
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“17”
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BackgroundSerum and Urinary Hepcidin for Diagnosing Iron-deficiency Anemia in Under-5 Children
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Serum Ferritin Levels: A Clinical Guide in Patients With Hair Loss
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“Funding: This article was supported Meanwhile, iron increases the secretion of ferritin, possibly via TRPML1-mediated exocytosis.”
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“21 Therefore, we determined the proportion of macrophages in the liver and lungs of mice and found that the proportion of macrophages in the experimental group with adverse reactions was significantly higher than that in the control group (Figure 3C).”
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“23,24 Macrophages use the lysosomal transport pathway for ferritin secretion, omitting ER-Golgi glycosylation.”
BackgroundOrgan siderosis and hemophagocytosis during acute graft-versus-host disease
Nogai, A., Shi, Y., Pérez-Hernández, D., Cordes, S., Mengwasser, J., Mertlitz, S., Riesner, K., Kalupa, M., Erdmann, J. ‐., Ziebig, R., et al. (2016) · Haematologica · doi:10.3324/haematol.2016.144519 · Cited by 9
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“Serum ferritin levels usually correlate with body iron status (Jacobs and Worwood 1975), but in conditions of inflammation, ferritin levels can also increase in the absence of iron overload (Torti and Torti 1994; Cohen et al. 2010).”
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“Ferritin levels are elevated in conditions such as iron overload, inflammation, infections, and liver diseases [38,39].”
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
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