ArticleBlood2022
Soluble uric acid inhibits β2 integrin-mediated neutrophil recruitment in innate immunity.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- The link between hyperuricemia and diabetes: insights from a quantitative analysis of scientific literature.Frontiers in endocrinology · 2024Pooled it
- Association of serum uric acid, gout with incident sepsis: a large population-based prospective cohort study from UK Biobank.Journal of intensive care · 2026Article
- Soluble uric acid suppresses neutrophil-mediated host defense in sepsis.Nature communications · 2026Article
- Uric Acid-Driven Biomarkers and Clinical Outcomes in Metastatic Pancreatic Cancer: A Multicenter Real-World Cohort Study.Diagnostics (Basel, Switzerland) · 2026Article
- Impact of sex on the association between neutrophil percentage-to-albumin ratio and mortality in perioperative patients with chronic kidney disease: a retrospective analysis of the INSPIRE database.Perioperative medicine (London, England) · 2026Article
- Neutrophils in Kidney Disease: Linking Neutrophil Function and Microenvironment to Therapeutic Targets.Journal of inflammation research · 2026Review
- From soluble uric acid to sodium urate crystal: immune metabolic inflammation driven by uric acid morphological transformation and mechanism-oriented therapy.Frontiers in immunology · 2026Review
- Relationship between admission serum uric acid to lymphocyte ratio and the risk of ischemic stroke recurrence and death: a prospective study.Journal of global health · 2025Article
- Neutrophils and NETs in kidney disease.Nature reviews. Nephrology · 2025Review
- Identifying early predictive and diagnostic biomarkers and exploring metabolic pathways for sepsis after trauma based on an untargeted metabolomics approach.Scientific reports · 2025Article
- Metabolomic and Cellular Mechanisms of Drug-Induced Ototoxicity and Nephrotoxicity: Therapeutic Implications of Uric Acid Modulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Purine metabolism-associated key genes depict the immune landscape in gout patients.Discover oncology · 2025Article
- Chronic kidney disease.Nature reviews. Disease primers · 2025Review
- Cross-sectional and longitudinal associations between pan-immune-inflammation value and serum uric acid.Frontiers in endocrinology · 2025Article
- Nuclear receptor 4A1 is critical for neutrophil-dependent pulmonary immunity toFrontiers in immunology · 2025Article
- Article
- Neutrophils-biology and diversity.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Review
- Not just sugar: metabolic control of neutrophil development and effector functions.Journal of leukocyte biology · 2024Review
- Serum Uric Acid Levels Associated with Outcomes of Neurodegenerative Disorders and Brain Health: Findings from the UK Biobank.The journal of nutrition, health & aging · 2024Article
- Article
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neutrophils are key players during host defense and sterile inflammation. Neutrophil dysfunction is a characteristic feature of the acquired immunodeficiency during kidney disease. We speculated that the impaired renal clearance of the intrinsic purine metabolite soluble uric acid (sUA) may account for neutrophil dysfunction. Indeed, hyperuricemia (HU, serum UA of 9-12 mg/dL) related or unrelated to kidney dysfunction significantly diminished neutrophil adhesion and extravasation in mice with crystal- and coronavirus-related sterile inflammation using intravital microscopy and an air pouch model. This impaired neutrophil recruitment was partially reversible by depleting UA with rasburicase. We validated these findings in vitro using either neutrophils or serum from patients with kidney dysfunction-related HU with or without UA depletion, which partially normalized the defective migration of neutrophils. Mechanistically, sUA impaired β2 integrin activity and internalization/recycling by regulating intracellular pH and cytoskeletal dynamics, physiological processes that are known to alter the migratory and phagocytic capability of neutrophils. This effect was fully reversible by blocking intracellular uptake of sUA via urate transporters. In contrast, sUA had no effect on neutrophil extracellular trap formation in neutrophils from healthy subjects or patients with kidney dysfunction. Our results identify an unexpected immunoregulatory role of the intrinsic purine metabolite sUA, which contrasts the well-known immunostimulatory effects of crystalline UA. Specifically targeting UA may help to overcome certain forms of immunodeficiency, for example in kidney dysfunction, but may enhance sterile forms of inflammation.
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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 OpenQuestion graph.