ArticleBlood2012
Mammalian target of rapamycin regulates neutrophil extracellular trap formation via induction of hypoxia-inducible factor 1 α.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 166 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
166 citing papers in PubMed, 2 syntheses or guidelines pooled it, 259 citations in OpenAlex.
- Thrombotic outcomes and mortality with roxadustat for anemia in chronic kidney disease: a systematic review and meta-analysis of randomized trials.Frontiers in pharmacology · 2026Pooled it
- In vitro induction of NETosis: Comprehensive live imaging comparison and systematic review.PloS one · 2017Pooled it
- Traumatic Injury and Exposure to Mitochondrial-Derived Damage Associated Molecular Patterns Suppresses Neutrophil Extracellular Trap Formation.Frontiers in immunology · 2019Trial
- Propofol Inhibits Neutrophil Extracellular Traps Formation and Alleviates Sepsis-Induced Acute Lung Injury.Inflammation · 2026Article
- Immunometabolic reprogramming and mitochondrial dysfunction in acute respiratory distress syndrome: mechanisms, metabolic resilience, and therapeutic perspectives- a narrative review.Journal of translational medicine · 2026Review
- The hypoxia-inflammation cycle as a key mechanism of smoldering inflammation and progression in multiple sclerosis.Acta neuropathologica · 2026Review
- The hypoxic ECM and neutrophils in MIBC immunotherapy resistance.Nature reviews. Urology · 2026Review
- Hypoxia-inducible factors contribute to venous thrombosis in a mouse model of myeloproliferative neoplasms.Blood advances · 2026Article
- Mitochondria-targeted nanozyme system for psoriasis treatment.Journal of nanobiotechnology · 2026Article
- The small-molecule Syk inhibitor R788 inhibits hematopoiesis and worsens anemia in sickle cell disease mice.Blood vessels, thrombosis & hemostasis · 2026Article
- Molecular subtyping and immune microenvironment heterogeneity in pediatric influenza-associated prolonged multiple organ dysfunction syndrome.Translational pediatrics · 2026Article
- Spatiotemporal dynamics of tumor-associated neutrophils: bridging the gap between cancer progression and immunotherapy.Molecular cancer · 2026Review
- Neutrophil extracellular traps in tumor microenvironment for radiotherapy: friend or foe?Frontiers in immunology · 2026Review
- The Paradox of NET Involvement in the Pathogenesis of Inflammatory Bowel Disease.Inflammatory bowel diseases · 2026Review
- Macrophage Hypoxia Signaling Pathways and Their Roles in Sepsis.Journal of inflammation research · 2026Review
- Lysine lactylation in neutrophil functional remodeling across diverse disease contexts.Frontiers in immunology · 2026Review
- Review
- Neutrophil immunometabolism in ACLF and sepsis: mechanisms, dysfunction, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Neutrophil extracellular traps in tumor metastasis: mechanisms, and therapeutic implications.Discover oncology · 2025Review
- Identification and analysis of neutrophil extracellular trap-related genes in periodontitis via bioinformatics and experimental verification.BMC oral health · 2025Article
106 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
Neutrophils are highly specialized innate immune effector cells that evolved for antimicrobial host defense. In response to inflammatory stimuli and pathogens, they form neutrophil extracellular traps (NETs), which capture and kill extracellular microbes. Deficient NET formation predisposes humans to severe infection, but, paradoxically, dysregulated NET formation contributes to inflammatory vascular injury and tissue damage. The molecular pathways and signaling mechanisms that control NET formation remain largely uncharacterized. Using primary human neutrophils and genetically manipulated myeloid leukocytes differentiated to surrogate neutrophils, we found that mammalian target of rapamycin (mTOR) regulates NET formation by posttranscriptional control of expression of hypoxia-inducible factor 1 α (HIF-1α), a critical modulator of antimicrobial defenses. Next-generation RNA sequencing, assays of mRNA and protein expression, and analysis of NET deployment by live cell imaging and quantitative histone release showed that mTOR controls NET formation and translation of HIF-1α mRNA in response to lipopolysaccharide. Pharmacologic and genetic knockdown of HIF-1α expression and activity inhibited NET deployment, and inhibition of mTOR and HIF-1α inhibited NET-mediated extracellular bacterial killing. Our studies define a pathway to NET formation involving 2 master regulators of immune cell function and identify potential points of molecular intervention in strategies to modify NETs in 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.