ArticlePloS one2012
Platelets induce apoptosis during sepsis in a contact-dependent manner that is inhibited by GPIIb/IIIa blockade.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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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
40 citing papers in PubMed, 64 citations in OpenAlex.
- Thromborepair: the tissue repair partner to thromboinflammation.Blood vessels, thrombosis & hemostasis · 2026Review
- Platelet extravasation in the microvasculature: an under-appreciated role for platelets.Frontiers in immunology · 2026Review
- Association Between Plasma Granzyme B Levels, Organ Failure, and 28-Day Mortality Prediction in Patients with Sepsis.Journal of clinical medicine · 2025Article
- The impact of platelets and antiplatelets medications on immune mediation.JVS-vascular science · 2025Review
- Megakaryocyte in sepsis: the trinity of coagulation, inflammation and immunity.Critical care (London, England) · 2024Review
- The relative importance of platelet integrins in hemostasis, thrombosis and beyond.Haematologica · 2023Review
- Current knowledge of thrombocytopenia in sepsis and COVID-19.Frontiers in immunology · 2023Review
- Preliminary Study on the Host Response to Bivalent and Monovalent Autogenous Vaccines againstVeterinary sciences · 2022Article
- Sepsis and Thrombocytopenia: A Nowadays Problem.Cureus · 2022Review
- Standardized fraction of Xylocarpus moluccensis inhibits inflammation by modulating MAPK-NFκB and ROS-HIF1α-PKM2 activation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Article
- Platelets differentially modulate CD4Immunologic research · 2022Article
- Platelet in thrombo-inflammation: Unraveling new therapeutic targets.Frontiers in immunology · 2022Review
- Experimental Models to Study the Pathogenesis of Malaria-Associated Acute Respiratory Distress Syndrome.Frontiers in cellular and infection microbiology · 2022Review
- Platelets in pediatric and neonatal sepsis: novel mediators of the inflammatory cascade.Pediatric research · 2022Review
- Platelet P2YTH open : companion journal to thrombosis and haemostasis · 2021Article
- Interaction Networks Converging on Immunosuppressive Roles of Granzyme B: Special Niches Within the Tumor Microenvironment.Frontiers in immunology · 2021Review
- Splenic Capture andACS nano · 2020Article
- Antiplatelet Therapy for Acute Respiratory Distress Syndrome.Biomedicines · 2020Review
- Haem oxygenase protects against thrombocytopaenia and malaria-associated lung injury.Malaria journal · 2020Article
- Antiplatelet Agents in Sepsis-Putting it all together: A Call to Action.Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
purposeEnd-organ apoptosis is well-described in progressive sepsis and Multiple Organ Dysfunction Syndrome (MODS), especially where platelets accumulate (e.g. spleen and lung). We previously reported an acute sepsis-induced cytotoxic platelet phenotype expressing serine protease granzyme B. We now aim to define the site(s) of and mechanism(s) by which platelet granzyme B induces end-organ apoptosis in sepsis.
methodsEnd-organ apoptosis in murine sepsis (i.e. polymicrobial peritonitis) was analyzed by immunohistochemistry. Platelet cytotoxicity was measured by flow cytometry following 90 minute ex vivo co-incubation with healthy murine splenocytes. Sepsis progression was measured via validated preclinical murine sepsis score. MEASUREMENTS AND MAIN
resultsThere was evident apoptosis in spleen, lung, and kidney sections from septic wild type mice. In contrast, there was a lack of TUNEL staining in spleens and lungs from septic granzyme B null mice and these mice survived longer following induction of sepsis than wild type mice. In co-incubation experiments, physical separation of septic platelets from splenocytes by a semi-permeable membrane reduced splenocyte apoptosis to a rate indistinguishable from negative controls. Chemical separation by the platelet GPIIb/IIIa receptor inhibitor eptifibatide decreased apoptosis by 66.6±10.6% (p = 0.008). Mice treated with eptifibatide in vivo survived longer following induction of sepsis than vehicle control mice.
conclusionsIn sepsis, platelet granzyme B-mediated apoptosis occurs in spleen and lung, and absence of granzyme B slows sepsis progression. This process proceeds in a contact-dependent manner that is inhibited ex vivo and in vivo by the platelet GPIIb/IIIa receptor inhibitor eptifibatide. The GPIIb/IIIa inhibitors and other classes of anti-platelet drugs may be protective in sepsis.
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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.