ArticleJournal of thrombosis and haemostasis : JTH2013
C560Rβ3 caused platelet integrin αII b β3 to bind fibrinogen continuously, but resulted in a severe bleeding syndrome and increased murine mortality.
Article in Journal of thrombosis and haemostasis : JTH, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Calmodulin Interaction Interface with Plasma Membrane CaInternational journal of molecular sciences · 2025Article
- A single F153Sβ3 mutation causes constitutive integrin αIIbβ3 activation in a variant form of Glanzmann thrombasthenia.Blood advances · 2023Article
- CD44-fibrinogen binding promotes bleeding in acute promyelocytic leukemia by in situ fibrin(ogen) deposition.Blood advances · 2022Article
- Toll-like Receptor 4, Osteoblasts and Leukemogenesis; the Lesson from Acute Myeloid Leukemia.Molecules (Basel, Switzerland) · 2022Review
- Genetic classification and confirmation of inherited platelet disorders: current status in Korea.Clinical and experimental pediatrics · 2020Article
- [Special type of Glanzmann's thrombasthenia].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2018Article
- Review
- Glanzmann thrombasthenia in Pakistan: molecular analysis and identification of novel mutations.Clinical genetics · 2016Article
- The role of Nox-mediated oxidation in the regulation of cytoskeletal dynamics.Current pharmaceutical design · 2015Review
- Internal relationship between symptomatic venous thromboembolism and risk factors: up-regulation of integrin β1, β2 and β3 levels.American journal of translational research · 2015Article
- Pro32Pro33 mutations in the integrin β3 PSI domain result in αIIbβ3 priming and enhanced adhesion: reversal of the hypercoagulability phenotype by the Src inhibitor SKI-606.Molecular pharmacology · 2014Article
- Increased expressions of integrin subunit β1, β2 and β3 in patients with venous thromboembolism: new markers for venous thromboembolism.International journal of clinical and experimental medicine · 2014Article
- Activation of circulated immune cells and inflammatory immune adherence are involved in the whole process of acute venous thrombosis.International journal of clinical and experimental medicine · 2014Article
- Glanzmann thrombasthenia: state of the art and future directions.Seminars in thrombosis and hemostasis · 2013Review
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
objectivesβ(3)-Deficient megakaryocytes were modified by human β(3)-lentivirus transduction and transplantation to express sufficient levels of a C560Rβ(3) amino acid substitution, for investigation of how an activated αII b β(3) conformation affects platelets in vivo in mice. PATIENT/
methodsAs in our previous report of an R560β(3) mutation in a patient with Glanzmann thrombasthenia, R560β(3) murine platelets spontaneously bound antibody that only recognizes activated αII b β3 bound to its ligand, fibrinogen.
resultsWith this murine model, we showed that αII b -R560β3 mutation-mediated continuous binding of fibrinogen occurred in the absence of P-selectin surface expression, indicating that the integrin was in an active conformation, although the platelets circulated in a quiescent manner. Remarkably, only 35% of R560β(3) 'mutant' mice survived for 6 months after transplantation, whereas 87% of C560β(3) 'wild-type' mice remained alive. Pathologic examination revealed that R560β(3) mice had enlarged spleens with extramedullary hematopoiesis and increased hemosiderin, indicating hemorrhage. R560β(3) megakaryocytes and platelets showed abnormal morphology and irregular granule distribution. Interestingly, R560β(3) washed platelets could aggregate upon simultaneous addition of fibrinogen and physiologic agonists, but aggregation failed when platelets were exposed to fibrinogen before activation in vitro and in vivo.
conclusionsThe results demonstrate that continuous occupancy of αIIb β3 with fibrinogen disrupts platelet structure and function, leading to hemorrhagic death consistent with Glanzmann thrombasthenia rather than a thrombotic state.
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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.