ArticleJournal of thrombosis and haemostasis : JTH2021
Platelet-conditioned media induces an anti-inflammatory macrophage phenotype through EP4.
Article in Journal of thrombosis and haemostasis : JTH, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Thromborepair: the tissue repair partner to thromboinflammation.Blood vessels, thrombosis & hemostasis · 2026Review
- Dynamic regulation and targeted interventions of macrophages in ischemia-reperfusion injury.Journal of advanced research · 2026Review
- Immunomodulation by platelet-derived DKK1: potential for controlling disease and pathology in leishmaniasis and implications for other infectious diseases.Frontiers in immunology · 2026Review
- Machine learning for prediction of histologic chorioamnionitis (stage ≥II) in parturients receiving labor analgesia: a retrospective multicentre cohort study.Frontiers in medicine · 2026Article
- Platelet-rich therapies in cutaneous and mucocutaneous disorders characterized by inflammatory tissue responses: mechanistic insights and clinical evidence.Frontiers in medicine · 2026Review
- Platelet activation stimulates macrophages to enhance ulcerative colitis through PF4/CXCR3 signaling.International journal of molecular medicine · 2025Article
- Platelet secretions exert anti-inflammatory effectsFrontiers in immunology · 2025Article
- Innovative Atherosclerosis Models: Advancing Pathophysiology and Translational Research.Research (Washington, D.C.) · 2025Review
- One immune cell to bind them all: platelet contribution to neurodegenerative disease.Molecular neurodegeneration · 2024Review
- Article
- Development and experimental validation of an M2 macrophage and platelet-associated gene signature to predict prognosis and immunotherapy sensitivity in bladder cancer.Cancer science · 2024Article
- Platelet, a key regulator of innate and adaptive immunity.Frontiers in medicine · 2023Review
- Platelet formation and activation are influenced by neuronal guidance proteins.Frontiers in immunology · 2023Review
- Functional Phenotypes of Intraplaque Macrophages and Their Distinct Roles in Atherosclerosis Development and Atheroinflammation.Biomedicines · 2022Review
- Wnt signaling enhances macrophage responses to IL-4 and promotes resolution of atherosclerosis.eLife · 2021Article
- Resolvin D1 Enhances Necroptotic Cell Clearance Through Promoting Macrophage Fatty Acid Oxidation and Oxidative Phosphorylation.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- CLEC-2 Prevents Accumulation and Retention of Inflammatory Macrophages During Murine Peritonitis.Frontiers in immunology · 2021Article
- The Provocative Roles of Platelets in Liver Disease and Cancer.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundPlatelets are increasingly recognized as immune cells. As such, they are commonly seen to induce and perpetuate inflammation; however, anti-inflammatory activities are increasingly attributed to them. Atherosclerosis is a chronic inflammatory condition. Similar to other inflammatory conditions, the resolution of atherosclerosis requires a shift in macrophages to an M2 phenotype, enhancing their efferocytosis and cholesterol efflux capabilities.
objectivesTo assess the effect of platelets on macrophage phenotype.
methodsIn several in vitro models employing murine (RAW264.7 and bone marrow-derived macrophages) and human (THP-1 and monocyte-derived macrophages) cells, we exposed macrophages to media in which non-agonized human platelets were cultured for 60 minutes (platelet-conditioned media [PCM]) and assessed the impact on macrophage phenotype and function.
resultsAcross models, we demonstrated that PCM from healthy humans induced a pro-resolving phenotype in macrophages. This was independent of signal transducer and activator of transcription 6 (STAT6), the prototypical pathway for M2 macrophage polarization. Stimulation of the EP4 receptor on macrophages by prostaglandin E2 present in PCM, is at least partially responsible for altered gene expression and associated function of the macrophages-specifically reduced peroxynitrite production, increased efferocytosis and cholesterol efflux capacity, and increased production of pro-resolving lipid mediators (ie, 15R-LXA
conclusionsPlatelet-conditioned media induces an anti-inflammatory, pro-resolving phenotype in macrophages. Our findings suggest that therapies targeting hemostatic properties of platelets, while not influencing pro-resolving, immune-related activities, could be beneficial for the treatment of atherothrombotic disease.
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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.