ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2022
Alarming and Calming: Opposing Roles of S100A8/S100A9 Dimers and Tetramers on Monocytes.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- A Nutrient-Sensitive ZRF1-Dependent Secretory Network Involving S100A9 Contributes to Neutrophil Plasticity in Triple-Negative Breast Cancer.ACS pharmacology & translational science · 2026Article
- Secreted protein combination GAPDH/S100A8/S100A9 from human expanded potential stem cells counteracts mesenchymal stromal cell senescence.Stem cell research & therapy · 2026Article
- A first structural model for covalent dimerization of S100 proteins.Acta crystallographica. Section F, Structural biology communications · 2026Article
- Design and characterization of calprotectin tetramerization variants for probing the role of oligomerization in receptor activation.Protein science : a publication of the Protein Society · 2026Article
- Chronic skin and systemic inflammation modulated by S100A8 and S100A9 complexes.Cell death and differentiation · 2025Article
- Shared Mechanisms in Cancer and Cardiovascular Disease: S100A8/9 and the NLRP3 Inflammasome: JACC: CardioOncology State-of-the-Art Review.JACC. CardioOncology · 2025Review
- S100A8 regulated by estrogen improves injured endometrial epithelium reconstruction by promoting tight junction formation and stromal cell transformation.Scientific reports · 2025Article
- TARGETING S100A9-TLR2 AXIS CONTROLS MACROPHAGE NLRP3 INFLAMMASOME ACTIVATION IN FATTY LIVER ISCHEMIA REPERFUSION INJURY.Shock (Augusta, Ga.) · 2025Article
- T cells in cardiac health and disease.The Journal of clinical investigation · 2025Review
- Effect of the S100A9/AMPK pathway on PM2.5-mediated mouse lung injury.Iranian journal of basic medical sciences · 2025Article
- S100A8/A9 high-expression macrophages mediate renal tubular epithelial cell damage in acute kidney injury following acute type A aortic dissection surgery.Frontiers in molecular biosciences · 2025Article
- The alarmin tandem: unraveling the complex effect of S100A8/A9 - from atherosclerosis to cardiac arrhythmias.Frontiers in immunology · 2025Review
- Cytosolic S100A8/A9 promotes CaeLife · 2024Article
- The role of the S100A8/S100A9 in gastric tumor progression.Scientific reports · 2024Article
- Unraveling the Mechanisms of S100A8/A9 in Myocardial Injury and Dysfunction.Current issues in molecular biology · 2024Review
- Single-Cell RNA Sequencing Reveals Immunomodulatory Effects of Stem Cell Factor and Granulocyte Colony-Stimulating Factor Treatment in the Brains of Aged APP/PS1 Mice.Biomolecules · 2024Article
- S100A9 exerts insulin-independent antidiabetic and anti-inflammatory effects.Science advances · 2024Article
- Blocking S100A9-signaling is detrimental to the initiation of anti-tumor immunity.Frontiers in immunology · 2024Article
- Changes in S100A8/A9 and S100A12 and Their Comparison with Other Analytes in the Saliva of Pigs with Diarrhea Due toAnimals : an open access journal from MDPI · 2023Article
- S-100 Proteins: Basics and Applications as Biomarkers in Animals with Special Focus on Calgranulins (S100A8, A9, and A12).Biology · 2023Review
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 4 countries.
Funding
Abstract
Mechanisms keeping leukocytes distant of local inflammatory processes in a resting state despite systemic release of inflammatory triggers are a pivotal requirement for avoidance of overwhelming inflammation but are ill defined. Dimers of the alarmin S100A8/S100A9 activate Toll-like receptor-4 (TLR4) but extracellular calcium concentrations induce S100A8/S100A9-tetramers preventing TLR4-binding and limiting their inflammatory activity. So far, only antimicrobial functions of released S100A8/S100A9-tetramers (calprotectin) are described. It is demonstrated that extracellular S100A8/S100A9 tetramers significantly dampen monocyte dynamics as adhesion, migration, and traction force generation in vitro and immigration of monocytes in a cutaneous granuloma model and inflammatory activity in a model of irritant contact dermatitis in vivo. Interestingly, these effects are not mediated by the well-known binding of S100A8/S100A9-dimers to TLR-4 but specifically mediated by S100A8/S100A9-tetramer interaction with CD69. Thus, the quaternary structure of these S100-proteins determines distinct and even antagonistic effects mediated by different receptors. As S100A8/S100A9 are released primarily as dimers and subsequently associate to tetramers in the high extracellular calcium milieu, the same molecules promote inflammation locally (S100-dimer/TLR4) but simultaneously protect the wider environment from overwhelming inflammation (S100-tetramer/CD69).
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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.