ArticleJournal of thrombosis and haemostasis : JTH2016
Dimerization of glycoprotein Ibα is not sufficient to induce platelet clearance.
Article in Journal of thrombosis and haemostasis : JTH, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Differential regulation of the platelet GPIb-IX complex by anti-GPIbβ antibodies.Journal of thrombosis and haemostasis : JTH · 2021Article
- GPIbα is the driving force of hepatic thrombopoietin generation.Research and practice in thrombosis and haemostasis · 2021Article
- Structure-function of platelet glycoprotein Ib-IX.Journal of thrombosis and haemostasis : JTH · 2020Review
- Platelet-specific antibodies and differences in their expression in childhood immune thrombocytopenic purpura predicts clinical progression.Pediatric investigation · 2018Article
- Effect of Pneumatic Tubing System Transport on Platelet Apheresis Units.Cardiovascular engineering and technology · 2018Article
- Review
- Only the strong: when antibodies hold on.Blood · 2018Article
- Article
- Glycans and the platelet life cycle.Platelets · 2016Review
- Inhibiting GPIbα Shedding Preserves Post-Transfusion Recovery and Hemostatic Function of Platelets After Prolonged Storage.Arteriosclerosis, thrombosis, and vascular biology · 2016Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
unlabelledESSENTIALS: Many anti-glycoprotein (GP)Ibα antibodies induce platelet clearance in a dimer-dependent manner. Characterization of monoclonal antibodies that bind the mechanosensitive domain (MSD) of GPIbα. An anti-MSD antibody binds two copies of GPIbα in platelets but does not induce platelet clearance. The prevailing clustering model of GPIbα signaling is incorrect or needs revision.
backgroundThe mechanism of platelet clearance is not clear. Many antibodies binding the membrane-distal ligand-binding domain of glycoprotein (GP)Ibα induce rapid clearance of platelets and acute thrombocytopenia, which requires the bifurcated antibody structure. It was thought that binding of these antibodies induced lateral dimerization or clustering of GPIbα in the plasma membrane, which leads to downstream signaling and platelet clearance. However, many antibodies targeting GPIbβ and GPIX, which are associated with GPIbα in the GPIb-IX complex, do not induce platelet clearance, which is in contradiction to the clustering model.
objectivesTo test whether dimerization or clustering of GPIbα is sufficient to transmit the signal that leads to platelet clearance.
methodsWe have recently raised several mAbs targeting the mechanosensitive domain (MSD) of GPIbα. Binding of these anti-MSD antibodies was characterized with biochemical methods. Their ability to stimulate platelets and induce platelet clearance in mice was assessed. RESULTS AND
conclusionInfusion of anti-MSD antibodies does not cause thrombocytopenia in mice. These antibodies show no detectable effects on platelet activation and aggregation in vitro. Further biochemical investigation showed that the anti-MSD antibody 3D1 binds two copies of GPIbα on the platelet surface. Therefore, lateral dimerization of GPIbα induced by antibody binding is not sufficient to initiate GPIb-IX signaling and induce platelet clearance. Our results suggest that a factor other than or in addition to clustering of GPIbα is required to induce platelet clearance.
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