ArticleJournal of leukocyte biology2014
LPS-induced systemic inflammation is more severe in P2Y12 null mice.
Article in Journal of leukocyte biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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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
53 citing papers in PubMed, 97 citations in OpenAlex.
- Platelets and inflammation-insights from platelet non-coding RNA content and release in the Bruneck study and the PACMAN-AMI trial.Cardiovascular research · 2025Trial
- Platelet P2Y12 Inhibitors Reduce Systemic Inflammation and Its Prothrombotic Effects in an Experimental Human Model.Arteriosclerosis, thrombosis, and vascular biology · 2015Trial
- Seasonality of Cytokines in Inflammatory Disease: Exploring Molecular Parallels with the Yellow Emperor's Inner Canon.Biology · 2026Review
- Platelet homeostasis and heterogeneity in inflammation and sepsis: mechanisms, biological effects, and clinical potential.Cell communication and signaling : CCS · 2026Review
- Time-restricted feeding in adult mice improves mood-related behaviors in a sex-dependent manner.Behavioural brain research · 2026Article
- A cecal slurry mouse model of polymicrobial abdominal sepsis to evaluate the effects of antiplatelet agents.Research and practice in thrombosis and haemostasis · 2026Article
- Prenatal exposure to polystyrene nanoparticles induces neuroimmune dysregulation in the adult mouse brain.Zoological research · 2025Article
- Acupuncture accelerates wound healing via CGRP-RAMP1-TSP1-mediated macrophage M2 polarization.Chinese medicine · 2025Article
- Observational
- Environmental temperature and immune activation during development: effects on organ growth in juvenile degus.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2025Article
- The Crucial Roles of Platelets as Immune Mediators in Sepsis.Journal of inflammation research · 2025Review
- Effects of Omega-3 Polyunsaturated Fatty Acids on the Formation of Adipokines, Cytokines, and Oxylipins in Retroperitoneal Adipose Tissue of Mice.International journal of molecular sciences · 2024Article
- Platelet P2YBritish journal of pharmacology · 2024Review
- Exploring immunoregulatory properties of a phenolic-enriched maple syrup extract through integrated proteomics andFood & function · 2024Article
- Purinergic Signaling and its Role in the Stem Cell Differentiation.Mini reviews in medicinal chemistry · 2024Review
- Spinal cord injury enhances lung inflammation and exacerbates immune response following exposure to LPS.Frontiers in immunology · 2024Article
- Low-quality protein modulates inflammatory markers and the response to lipopolysaccharide insult: the case of lysine.The British journal of nutrition · 2023Article
- Article
- Platelets and platelet-derived vesicles as an innovative cellular and subcellular platform for managing multiple sclerosis.Molecular biology reports · 2023Review
- A Whey-Based Diet Can Ameliorate the Effects of LPS-Induced Growth Attenuation in Young Rats.Nutrients · 2023Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Thienopyridines are a class of antiplatelet drugs that are metabolized in the liver to several metabolites, of which only one active metabolite can irreversibly antagonize the platelet P2Y12 receptor. Possible effects of these drugs and the role of activated platelets in inflammatory responses have also been investigated in a variety of animal models, demonstrating that thienopyridines could alter inflammation. However, it is not clear whether it is caused only by the P2Y12 antagonism or whether off-target effects of other metabolites also intervene. To address this question, we investigated P2Y12 KO mice during a LPS-induced model of systemic inflammation, and we treated these KO mice with a thienopyridine drug (clopidogrel). Contrary to the reported effects of clopidogrel, numbers of circulating WBCs and plasma levels of cytokines were increased in LPS-exposed KO mice compared with WT in this inflammation model. Moreover, both spleen and bone marrow show an increase in cell content, suggesting a role for P2Y12 in regulation of bone marrow and spleen cellular composition. Finally, the injury was more severe in the lungs of KO mice compared with WT. Interestingly, clopidogrel treatments also exerted protective effects in KO mice, suggesting off-target effects for this drug. In conclusion, the P2Y12 receptor plays an important role during LPS-induced inflammation, and this signaling pathway may be involved in regulating cell content in spleen and bone marrow during LPS systemic inflammation. Furthermore, clopidogrel may have effects that are independent of P2Y12 receptor blockade.
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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.