ArticleThrombosis and haemostasis2009
Immune versus thrombotic stimulation of platelets differentially regulates signalling pathways, intracellular protein-protein interactions, and alpha-granule release.
Article in Thrombosis and haemostasis, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed, 109 citations in OpenAlex.
- Trial
- Characterization of Platelet Receptors and Their Involvement in Immune Activation of These Cells.International journal of molecular sciences · 2024Review
- Activated platelets retain and protect most of their factor XIII-A cargo from proteolytic activation and degradation.Blood advances · 2024Article
- Platelets in Alcohol-Associated Liver Disease: Interaction With Neutrophils.Cellular and molecular gastroenterology and hepatology · 2024Review
- Toll-like Receptors and Thrombopoiesis.International journal of molecular sciences · 2023Review
- Liver cirrhosis and complications from the perspective of dysbiosis.Frontiers in medicine · 2023Review
- Platelet Reactivity and Inflammatory Phenotype Induced by Full-Length Spike SARS-CoV-2 Protein and Its RBD Domain.International journal of molecular sciences · 2022Article
- Factors Associated with Platelet Activation-Recent Pharmaceutical Approaches.International journal of molecular sciences · 2022Review
- Platelet-Derived Drug Targets and Biomarkers of Ischemic Stroke-The First Dynamic Human LC-MS Proteomic Study.Journal of clinical medicine · 2022Article
- Mechanism and Potential Target of Blood-Activating Chinese Botanical Drugs Combined With Anti-Platelet Drugs: Prevention and Treatment of Atherosclerotic Cardiovascular Diseases.Frontiers in pharmacology · 2022Review
- Platelets in pediatric and neonatal sepsis: novel mediators of the inflammatory cascade.Pediatric research · 2022Review
- Inflammatory Mediators of Platelet Activation: Focus on Atherosclerosis and COVID-19.International journal of molecular sciences · 2021Review
- Thrombosis in COVID-19 infection: Role of platelet activation-mediated immunity.Thrombosis journal · 2021Review
- Role of Thrombin in Central Nervous System Injury and Disease.Biomolecules · 2021Review
- Platelet Proteomes, Pathways, and Phenotypes as Informants of Vascular Wellness and Disease.Arteriosclerosis, thrombosis, and vascular biology · 2021Review
- GP IIb/IIIa-Mediated Platelet Activation and Its Modulation of the Immune Response of Monocytes AgainstFrontiers in cellular and infection microbiology · 2021Article
- Revisiting Platelets and Toll-Like Receptors (TLRs): At the Interface of Vascular Immunity and Thrombosis.International journal of molecular sciences · 2020Review
- The gut microbiome and thromboembolism.Thrombosis research · 2020Review
- Proteomic Profiling of Plasma and Brain Tissue from Alzheimer's Disease Patients Reveals Candidate Network of Plasma Biomarkers.Journal of Alzheimer's disease : JAD · 2020Article
- Platelet Toll-Like Receptors Mediate Thromboinflammatory Responses in Patients With Essential Thrombocythemia.Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
In addition to haemostasis, platelets mediate inflammation and clearance of bacteria from the bloodstream. As with platelet-platelet interactions, platelet-bacteria interactions involve cytoskeletal rearrangements and release of granular content. Stimulation of the immune Toll-like receptor 2 (TLR2) on the platelet surface, activates phosphoinositide-3-kinase (PI3K) and causes platelet activation and platelet-dependent thrombosis. It remains unknown if platelet activation by immune versus thrombotic pathways leads to the differential regulation of signal transduction, protein-protein interactions, and alpha-granule release, and the physiological relevance of these potential differences. We investigated these processes after immune versus thrombotic platelet stimulation. We examined selected signalling pathways and found that phosphorylation kinetics of Akt, ERK1/2 and p38 differed dramatically between agonists. Next, we investigated platelet protein-protein interactions by mass spectrometry (MS)-based proteomics specifically targeting cytosolic factor XIIIa (FXIIIa) because of its function as a cytoskeleton-crosslinking protein whose binding partners have limited characterisation. Four FXIIIa-binding proteins were identified, two of which are novel interactions: FXIIIa-focal adhesion kinase (FAK) and FXIIIa-gelsolin. The binding of FAK to FXIIIa was found to be altered differentially by immune versus thrombotic stimulation. Lastly, we studied the effect of thrombin versus Pam(3)CSK(4) stimulation on alpha-granule release and observed differential release patterns for selected granule proteins and decreased fibrin clot formation compared with thrombin. The inhibition of PI3K caused a decrease in protein release after Pam(3)CSK(4)- but not after thrombin-stimulation. In summary, stimulation of platelets by either thrombotic or immune receptors leads to markedly different signalling responses and granular protein release consistent with differential contribution to coagulation and thrombosis.
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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.