ArticleProceedings of the National Academy of Sciences of the United States of America2018
Platelets release pathogenic serotonin and return to circulation after immune complex-mediated sequestration.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 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
118 citing papers in PubMed, 2 syntheses or guidelines pooled it, 217 citations in OpenAlex.
- Psychotropic drug repurposing for COVID-19: A Systematic Review and Meta-Analysis.European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2023Pooled it
- Efficacy and Safety of Recombinant Human Thrombopoietin on Sepsis Patients With Thrombocytopenia: A Systematic Review and Meta-Analysis.Frontiers in pharmacology · 2020Pooled it
- Immune-mediated platelet refractoriness: Mechanisms, diagnostics, and therapeutic breakthroughs.Transfusion medicine (Oxford, England) · 2026Review
- Megakaryocytes Internalize and Are Activated by Immune Complexes.Circulation research · 2026Article
- Fibrinogen-associated plasma metabolites and implications for coagulation, inflammation, and vascular diseases.Journal of thrombosis and haemostasis : JTH · 2026Article
- Immobilized IgG-containing immune complexes require platelets to recruit neutrophils during inflammation.The Journal of clinical investigation · 2026Article
- Clinical application of the HALP score for predicting early neurological deterioration in older patients with acute cerebral infarction.Biomedical reports · 2026Article
- Targeting macrophages prevents alloantibody-mediated platelet clearance in a murine model of transfusion refractoriness.Blood advances · 2026Article
- Role of central and peripheral serotonin in liver physiology and diseases.Theranostics · 2026Review
- Platelet activation, aspirin, and cancer: From basic science to clinical trials.Pharmacological reviews · 2026Review
- Platelet-mediated activation of perivascular mast cells triggers progression of sepsis to septic shock in mice.Nature communications · 2025Article
- Article
- Perturbed pediatric circulating metabolome in mild and severe dengue disease.Journal of virology · 2025Article
- Persistent Chronic Thrombo-Inflammation in Anti-Glomerular Basement Membrane Disease Despite Immune Complex Removal.Kidney international reports · 2025Article
- Narrating the psychoneuroimmunomodulatory properties of serotonin 5-HTActa neuropsychiatrica · 2025Review
- Anti-bacterial activity of dermcidin in human platelets: suppression of methicillin-resistantMicrobiology spectrum · 2025Article
- Flavanones as Modulators of Gut Microbiota and Cognitive Function.Molecules (Basel, Switzerland) · 2025Review
- Delayed viral clearance and altered inflammatory responses affect severity of SARS-CoV-2 infection in aged mice.Immunity & ageing : I & A · 2025Article
- Alterations in the Processing of Platelet APP (Amyloid Beta Precursor Protein) in Alzheimer Disease: The Possible Nexus.Neuropsychopharmacology reports · 2025Review
- Pathogenic and Nonpathogenic Antibody Responses in Allergic Diseases.European journal of immunology · 2025Review
58 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
24 authors at 8 institutions in 3 countries.
Funding
Abstract
There is a growing appreciation for the contribution of platelets to immunity; however, our knowledge mostly relies on platelet functions associated with vascular injury and the prevention of bleeding. Circulating immune complexes (ICs) contribute to both chronic and acute inflammation in a multitude of clinical conditions. Herein, we scrutinized platelet responses to systemic ICs in the absence of tissue and endothelial wall injury. Platelet activation by circulating ICs through a mechanism requiring expression of platelet Fcγ receptor IIA resulted in the induction of systemic shock. IC-driven shock was dependent on release of serotonin from platelet-dense granules secondary to platelet outside-in signaling by αIIbβ3 and its ligand fibrinogen. While activated platelets sequestered in the lungs and leaky vasculature of the blood-brain barrier, platelets also sequestered in the absence of shock in mice lacking peripheral serotonin. Unexpectedly, platelets returned to the blood circulation with emptied granules and were thereby ineffective at promoting subsequent systemic shock, although they still underwent sequestration. We propose that in response to circulating ICs, platelets are a crucial mediator of the inflammatory response highly relevant to sepsis, viremia, and anaphylaxis. In addition, platelets recirculate after degranulation and sequestration, demonstrating that in adaptive immunity implicating antibody responses, activated platelets are longer lived than anticipated and may explain platelet count fluctuations in IC-driven diseases.
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What OpenQuestion holds
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.