ArticleNature metabolism2025
Classically activated macrophages undergo functionally significant nucleotide metabolism remodelling driven by nitric oxide.
Article in Nature metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed.
- Probiotic extracellular vesicles reprogram macrophage immunometabolism: From gut crosstalk to host health.Gut microbes · 2026Review
- Kiss and spit metabolomics highlight the role of host purine metabolism during pathogen infection.mSphere · 2026Article
- Metabolomics ofbioRxiv : the preprint server for biology · 2026Article
- Multi-omic analysis reveals nitric oxide dependent remodeling in classically activated macrophages and identifies negative regulation mediated by AKR1A1.Redox biology · 2026Article
- Asymmetric nanozymes improve cardiac purine catabolism and alleviate oxidative stress of myocardium to treat ischemic heart disease.Journal of nanobiotechnology · 2026Article
- IMP metabolic mechanisms and IMPDH targeting strategies in tumor metabolic reprogramming and therapy (Review).International journal of molecular medicine · 2026Review
- Discovery of metabolites produced by reactions between central carbon metabolites and cysteine that mark inflammatory macrophages.bioRxiv : the preprint server for biology · 2026Article
- Total synthesis of marine cyclopeptide largamides B and H, and tiglicamide B.Molecular diversity · 2026Article
- Article
- Multi-omic analysis reveals nitric oxide dependent remodeling in classically activated macrophages and identifies negative regulation mediated by AKR1A1.bioRxiv : the preprint server for biology · 2026Article
- Mechanisms and therapeutic prospects of DNA methylation-mucosal innate immunity crosstalk in inflammatory bowel disease.Frontiers in immunology · 2026Review
- Macrophage-mediated nutrient recycling: evolutionary insights into the metabolic role of professional phagocytes.Frontiers in immunology · 2026Review
- Natural polysaccharides as multifunctional anti-cancer agents: structure-activity relationships, mechanisms of action, and therapeutic potential.Frontiers in immunology · 2026Review
- Oxidative stress-driven epigenetic reprogramming of immune cells in COPD: from epitranscriptomic and metabolic crosstalk to treatable traits.Frontiers in immunology · 2026Review
- Glycolytic reprogramming and immune responses in macrophages: a crosstalk driven by bacterial infection.Frontiers in immunology · 2026Review
- Neoepitopes at the crossroads of immunometabolism: metabolic remodeling of antigen presentation in type 1 diabetes.Frontiers in immunology · 2026Review
- Identification and characterization of senescent macrophages in renal allograft rejection: a cross-species MultiOmics study.Frontiers in immunology · 2025Article
- Breast milk-saliva interactions in shaping early mucosal immunity.Frontiers in immunology · 2025Review
- Integrated transcriptomic and metabolomic analysis reveals the effects of EMMPRIN on nucleotide metabolism and 1C metabolism in AS mouse BMDMs.Frontiers in molecular biosciences · 2024Article
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15 authors.
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Abstract
During an immune response, macrophages specifically reprogramme their metabolism to support functional changes. Here, we revealed that nucleotide metabolism is one of the most significantly reprogrammed pathways upon classical activation. Specifically, de novo synthesis of pyrimidines is maintained up to uridine monophosphate, but blocked at cytidine triphosphate and deoxythymidine monophosphate synthesis; de novo synthesis of purines is shut off at the last step (catalysed by AICAR transformylase/IMP cyclohydrolase, ATIC), and cells switch to increased purine salvage. Nucleotide degradation to nitrogenous bases is upregulated but complete oxidation of purine bases (catalysed by xanthine oxidoreductase, XOR) is inhibited, diverting flux into salvage. Mechanistically, nitric oxide was identified as a major regulator of nucleotide metabolism, simultaneously driving multiple key changes, including the transcriptional downregulation of Tyms and profound inhibition of ATIC and XOR. Inhibiting purine salvage using Hgprt knockout or inhibition alters the expression of many stimulation-induced genes, suppresses macrophage migration and phagocytosis, and increases the proliferation of the intracellular parasite Toxoplasma gondii. Together, these results thoroughly uncover the dynamic reprogramming of macrophage nucleotide metabolism upon classical activation and elucidate the regulatory mechanisms and functional significance of such reprogramming.
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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 Socratic graph.