ArticleJournal of thrombosis and haemostasis : JTH2015
Intramedullary megakaryocytes internalize released platelet factor 4 and store it in alpha granules.
Article in Journal of thrombosis and haemostasis : JTH, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Unveiling the "Dark Matter" of platelet involvement in tumor microenvironment.Journal of pharmaceutical analysis · 2025Review
- Article
- Serglycin controls megakaryocyte retention of platelet factor 4 and influences megakaryocyte fate in bone marrow.Blood advances · 2025Article
- The winding road to platelet α-granules.Frontiers in cell and developmental biology · 2025Review
- Megakaryocyte Secreted Factors Regulate Bone Marrow Niche Cells During Skeletal Homeostasis, Aging, and Disease.Calcified tissue international · 2023Review
- FLAN: feature-wise latent additive neural models for biological applications.Briefings in bioinformatics · 2023Article
- Benzo[a]pyrene Exposure Reduces Cell-Type Diversity and Stimulates Sex-Biased Damage Pathways in End Organs of Lupus-Prone Mice.International journal of molecular sciences · 2023Article
- The levels of TGFβ1, VEGF, PDGF-BB, and PF4 in platelet-rich plasma of professional soccer players: a cross-sectional pilot study.Journal of orthopaedic surgery and research · 2022Article
- COMManding platelet α-granule cargo.Blood · 2022Article
- Platelet Membrane: An Outstanding Factor in Cancer Metastasis.Membranes · 2022Review
- Megakaryocytes as immune cells.Journal of leukocyte biology · 2019Review
- Article
- Platelets Can Soak It Up and Then Spit It Out.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Phosphatidylinositol transfer proteins regulate megakaryocyte TGF-β1 secretion and hematopoiesis in mice.Blood · 2018Article
- 2-O, 3-O desulfated heparin mitigates murine chemotherapy- and radiation-induced thrombocytopenia.Blood advances · 2018Article
- Platelet-inspired medicine for tumor therapy.Oncotarget · 2017Review
- Platelet-Specific Chemokines Contribute to the Pathogenesis of Acute Lung Injury.American journal of respiratory cell and molecular biology · 2017Article
- Platelet Factor 4 Inhibits and Enhances HIV-1 Infection in a Concentration-Dependent Manner by Modulating Viral Attachment.AIDS research and human retroviruses · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundMegakaryocytes express and store platelet factor 4 (PF4) in alpha granules. In vivo, PF4 is a clinically relevant, negative regulator of megakaryopoiesis and hematopoietic stem cell replication. These findings would suggest a regulated source of free intramedullary PF4.
objectivesDefine the source of free intramedullary PF4 and its intramedullary life cycle.
methodsWe interrogated both murine and human bone marrow-derived cells during megakaryopoiesis in vitro by using confocal microscopy and enzyme-linked immunosorbent assay. With immunohistochemistry, we examined in vivo free PF4 in murine bone marrow before and after radiation injury and in the setting of megakaryocytopenia and thrombocytopenia.
resultsExogenously added human PF4 is internalized by murine megakaryocytes. Human megakaryocytes similarly take up murine PF4 but not the related chemokine, platelet basic protein. Confocal microscopy shows that internalized PF4 colocalizes with endogenous PF4 in alpha granules and is available for release on thrombin stimulation. Immunohistochemistry shows free PF4 in the marrow, but not another alphagranule protein, von Willebrand factor. Free PF4 increases with radiation injury and decreases with megakaryocytopenia. Consistent with the known role of low-density lipoprotein receptor-related protein 1 in the negative paracrine effect of PF4 on megakaryopoiesis, PF4 internalization is at least partially low-density lipoprotein receptor-related protein 1 dependent.
conclusionsPF4 has a complex intramedullary life cycle with important implications in megakaryopoiesis and hematopoietic stem cell replication not seen with other tested alpha granule proteins.
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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.