ArticleBlood2016
Hemopexin therapy reverts heme-induced proinflammatory phenotypic switching of macrophages in a mouse model of sickle cell disease.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 164 papers.
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Who cites it
164 citing papers in PubMed, 262 citations in OpenAlex.
- Sickle cell microvascular paradox-oxygen supply-demand mismatch.American journal of hematology · 2019Trial
- Inhaled steroids associated with decreased macrophage markers in nonasthmatic individuals with sickle cell disease in a randomized trial.Annals of hematology · 2019Trial
- Tissue-Resident Macrophages: Linking Physiology and Inflammation in Infection.Clinical reviews in allergy & immunology · 2026Review
- Apohemoglobin-haptoglobin complex is a therapeutic against vaso-occlusive crisis: scavenging of hemoglobin and heme.Blood advances · 2026Article
- Effect of clinically relevant iron oxide nanoparticles on macrophage polarization, tumor growth and tumor microenvironment modulation.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
- Regulation of mitochondrial iron homeostasis in tumor cells.Molecular medicine (Cambridge, Mass.) · 2026Review
- Iron and metabolic rewiring in cancer.Oncogenesis · 2026Review
- Iron Dyshomeostasis and Divergent Antigen Presentation Remodeling in Bronchiectasis: A Dual-Dataset Transcriptomic Analysis.Journal of inflammation research · 2026Article
- Selective AMPKβ1 activation induces fetal hemoglobin in human erythroid cells and sickle cell mice via the noncanonical NRF2 pathway.Science advances · 2025Article
- ISCU-p53 axis orchestrates macrophage polarization to dictate immunotherapy response in esophageal squamous cell carcinoma.Cell death & disease · 2025Article
- A clinical predictive score of high liver iron content in metabolic hyperferritinemia: a retrospective cohort pilot study.BMC gastroenterology · 2025Article
- Hepatocyte Toll-like receptors contribute to the hepcidin inflammatory response to pathogens and pathogen-derived ligands.HemaSphere · 2025Article
- Heme promotes venetoclax resistance in multiple myeloma through MEK-ERK signaling and purine biosynthesis.Blood · 2025Article
- Iron, Hepcidin, and Immunity.Advances in experimental medicine and biology · 2025Review
- Fresh autologous blood transfusion reverses erythrocyte damage by reducing oxidative stress via promoting mitochondrial metabolism and M2 macrophage polarization.Archives of medical science : AMS · 2025Article
- Depletion of macrophages and osteoclast precursors mitigates iron overload-mediated bone loss.IUBMB life · 2025Article
- Tracking hemopexin intracellularly and defining hemopexin protein "interactomes" in human immune and liver cell models.Frontiers in physiology · 2025Article
- Article
- Review
- Deficiency of the Hemoglobin-Haptoglobin Receptor, CD163, Worsens Insulin Sensitivity in Obese Male Mice.Diabetes · 2024Article
104 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
Abstract
Hemolytic diseases, such as sickle cell anemia and thalassemia, are characterized by enhanced release of hemoglobin and heme into the circulation, heme-iron loading of reticulo-endothelial system macrophages, and chronic inflammation. Here we show that in addition to activating the vascular endothelium, hemoglobin and heme excess alters the macrophage phenotype in sickle cell disease. We demonstrate that exposure of cultured macrophages to hemolytic aged red blood cells, heme, or iron causes their functional phenotypic change toward a proinflammatory state. In addition, hemolysis and macrophage heme/iron accumulation in a mouse model of sickle disease trigger similar proinflammatory phenotypic alterations in hepatic macrophages. On the mechanistic level, this critically depends on reactive oxygen species production and activation of the Toll-like receptor 4 signaling pathway. We further demonstrate that the heme scavenger hemopexin protects reticulo-endothelial macrophages from heme overload in heme-loaded Hx-null mice and reduces production of cytokines and reactive oxygen species. Importantly, in sickle mice, the administration of human exogenous hemopexin attenuates the inflammatory phenotype of macrophages. Taken together, our data suggest that therapeutic administration of hemopexin is beneficial to counteract heme-driven macrophage-mediated inflammation and its pathophysiologic consequences in sickle cell disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.