ArticleBlood2020
Macrophage metabolic adaptation to heme detoxification involves CO-dependent activation of the pentose phosphate pathway.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- The Role of the Pentose Phosphate Pathway in Cardiovascular Diseases.Cardiovascular drugs and therapy · 2026Review
- Apohemoglobin-haptoglobin complex is a therapeutic against vaso-occlusive crisis: scavenging of hemoglobin and heme.Blood advances · 2026Article
- Iron, arginine, and redox metabolism in peripheral blood mononuclear cells distinguishes sickle cell disease and pulmonary hypertension.HemaSphere · 2026Article
- The mechanisms by which free heme exacerbates sepsis and the potential therapeutic targets.Frontiers in immunology · 2026Review
- Microvesicle-transferred mitochondria trigger cGAS-STING and reprogram metabolism of macrophages in sepsis.Microbiology spectrum · 2025Article
- From metabolomics to transfusion-associated immunomodulation.Current opinion in immunology · 2025Review
- Heme and immunity: The heme oxygenase dichotomy.Journal of inorganic biochemistry · 2025Review
- The role of heme in sepsis induced Kupffer cell PANoptosis and senescence.Cell death & disease · 2025Article
- The clinical relevance of heme detoxification by the macrophage heme oxygenase system.Frontiers in immunology · 2024Review
- Hemorrhage-activated NRF2 in tumor-associated macrophages drives cancer growth, invasion, and immunotherapy resistance.The Journal of clinical investigation · 2023Article
- The pentose phosphate pathway in health and disease.Nature metabolism · 2023Review
- Article
- Role of Macrophages in Sickle Cell Disease Erythrophagocytosis and Erythropoiesis.International journal of molecular sciences · 2023Review
- Article
- Temporal changes in glucose metabolism reflect polarization in resident and monocyte-derived macrophages after myocardial infarction.Frontiers in cardiovascular medicine · 2023Article
- Macrophage acetyl-CoA carboxylase regulates acute inflammation through control of glucose and lipid metabolism.Science advances · 2022Article
- Article
- Transcriptional repression shapes the identity and function of tissue macrophages.FEBS open bio · 2021Review
- Macrophages and Iron: A Special Relationship.Biomedicines · 2021Review
- Iron Availability in Tissue Microenvironment: The Key Role of Ferroportin.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Heme is an essential cofactor for numerous cellular functions, but release of free heme during hemolysis results in oxidative tissue damage, vascular dysfunction, and inflammation. Macrophages play a key protective role in heme clearance; however, the mechanisms that regulate metabolic adaptations that are required for effective heme degradation remain unclear. Here we demonstrate that heme loading drives a unique bioenergetic switch in macrophages, which involves a metabolic shift from oxidative phosphorylation toward glucose consumption. Metabolomic and transcriptional analysis of heme-loaded macrophages revealed that glucose is funneled into the pentose phosphate pathway (PPP), which is indispensable for efficient heme detoxification and is required to maintain redox homeostasis. We demonstrate that the metabolic shift to the PPP is controlled by heme oxygenase-dependent generation of carbon monoxide (CO). Finally, we show that PPP upregulation occurs in vivo in organ systems central to heme clearance and that PPP activity correlates with heme levels in mouse sickle cell disease (SCD). Together, our findings demonstrate that metabolic adaptation to heme detoxification in macrophages requires a shift to the PPP that is induced by heme-derived CO, suggesting pharmacologic targeting of macrophage metabolism as a novel therapeutic strategy to improve heme clearance in patients with hemolytic disorders.
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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.