ArticleAmerican journal of physiology. Cell physiology2012
Differential activation of RAGE by HMGB1 modulates neutrophil-associated NADPH oxidase activity and bacterial killing.
Article in American journal of physiology. Cell physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- The impact of RAGE inhibition in animal models of bacterial sepsis: a systematic review and meta-analysis.The Journal of international medical research · 2018Pooled it
- Human resistin promotes neutrophil proinflammatory activation and neutrophil extracellular trap formation and increases severity of acute lung injury.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Neutrophil extracellular traps induced by activated platelets as a cause of neutrophil-platelet aggregation in β-thalassaemia/haemoglobin E patients.British journal of haematology · 2026Article
- RAGE in Neutrophils: A Sensor for Pathogen-Associated Structures and Beyond.Biomedicines · 2026Article
- Platelets as drivers of immunothrombosis in rheumatic diseases.Nature reviews. Rheumatology · 2025Review
- Pathophysiological Role of Neutrophil Extracellular Traps in Diet-Induced Obesity and Metabolic Syndrome in Animal Models.Nutrients · 2025Review
- Targeting the AGEs-RAGE axis: pathogenic mechanisms and therapeutic interventions in diabetic wound healing.Frontiers in medicine · 2025Review
- Neutrophil-Derived Proteases in Lung Inflammation: Old Players and New Prospects.International journal of molecular sciences · 2024Review
- Advanced Glycation End Products (AGEs) in Diet and Skin in Relation to Stool Microbiota: The Rotterdam Study.Nutrients · 2023Article
- HMGB1, angel or devil, in ischemic stroke.Brain and behavior · 2023Review
- HMGB1 is a critical molecule in the pathogenesis of Gram-negative sepsis.Journal of intensive medicine · 2022Review
- Cough hypersensitivity in patients with metabolic syndrome: a clinical finding and its possible mechanisms.BMC pulmonary medicine · 2021Article
- Bioenergetic maladaptation and release of HMGB1 in calcineurin inhibitor-mediated nephrotoxicity.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Article
- Review
- Ion and Water Transport in Neutrophil Granulocytes and Its Impairment during Sepsis.International journal of molecular sciences · 2021Review
- The impact of neutrophil extracellular trap from patients with systemic lupus erythematosus on the viability, CD11b expression and oxidative burst of healthy neutrophils.BMC immunology · 2021Article
- Advanced glycation end products (AGEs) synergistically potentiated the proinflammatory action of lipopolysaccharide (LPS) and high mobility group box-1 (HMGB1) through their direct interactions.Molecular biology reports · 2020Article
- The Receptor for Advanced Glycation Endproducts (RAGE) Contributes to Severe Inflammatory Liver Injury in Mice.Frontiers in immunology · 2020Article
- The Regulatory Role of High-Mobility Group Protein 1 in Sepsis-Related Immunity.Frontiers in immunology · 2020Review
- High-mobility group box1 as an amplifier of immune response and target for treatment inInternational journal of ophthalmology · 2020Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
The receptor for advanced glycation end products (RAGE) plays an important role in host defense against bacterial infection. In the present experiments, we investigated the mechanisms by which RAGE contributes to the ability of neutrophils to eradicate bacteria. Wild-type (RAGE(+/+)) neutrophils demonstrated significantly greater ability to kill Escherichia coli compared with RAGE(-/-) neutrophils. After intraperitoneal injection of E. coli, increased numbers of bacteria were found in the peritoneal fluid from RAGE(-/-) as compared with RAGE(+/+) mice. Exposure of neutrophils to the protypical RAGE ligand AGE resulted in activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and enhanced killing of E. coli, and intraperitoneal injection of AGE enhanced bacterial clearance during peritonitis. However, incubation of neutrophils with high mobility group box 1 protein (HMGB1), which also binds to RAGE, diminished E. coli-induced activation of NADPH oxidase in neutrophils and bacterial killing both in vitro and in vivo. Deletion of the COOH-terminal tail of HMGB1, a region necessary for binding to RAGE, abrogated the ability of HMGB1 to inhibit bacterial killing. Incubation of neutrophils with HMGB1 diminished bacterial or AGE-dependent activation of NADPH oxidase. The increase in phosphorylation of the p40(phox) subunit of NADPH oxidase that occurred after culture of neutrophils with E. coli was inhibited by exposure of the cells to HMGB1. These results showing that HMGB1, through RAGE-dependent mechanisms, diminishes bacterial killing by neutrophils as well as NADPH oxidase activation provide a novel mechanism by which HMGB1 can potentiate sepsis-associated organ dysfunction and mortality.
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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.