CD44 sensitivity of platelet activation, membrane scrambling and adhesion under high arterial shear rates
| العنوان: | CD44 sensitivity of platelet activation, membrane scrambling and adhesion under high arterial shear rates |
|---|---|
| المؤلفون: | Florian Lang, Meinrad Gawaz, Oliver Borst, Tak Z. Mak, Michael Föller, Jakob Voelkl, Hong Chen, Bernat Elvira, Anja T. Umbach, Dong Luo, Patrick Münzer, Britta Walker, Madhumita Chatterjee, Kousi Alzoubi, Guilai Liu, Guoxing Liu |
| المصدر: | Thrombosis and Haemostasis. 115:99-108 |
| بيانات النشر: | Georg Thieme Verlag KG, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Blood Platelets, Male, 0301 basic medicine, Genotype, ORAI1 Protein, Integrin, Apoptosis, Platelet Glycoprotein GPIIb-IIIa Complex, Biology, Ferric Compounds, Mechanotransduction, Cellular, Cell Degranulation, 03 medical and health sciences, Platelet Adhesiveness, 0302 clinical medicine, Thrombin, Chlorides, Platelet degranulation, Selenoprotein P, Platelet adhesiveness, medicine, Animals, Platelet, Calcium Signaling, Platelet activation, Mean platelet volume, Blood Coagulation, Phospholipids, Mice, Knockout, Caspase 3, Cell Membrane, Thrombosis, Hematology, Molecular biology, Disease Models, Animal, Hyaluronan Receptors, Phenotype, 030104 developmental biology, Biochemistry, Regional Blood Flow, 030220 oncology & carcinogenesis, biology.protein, Female, Calcium Channels, Stress, Mechanical, medicine.drug |
| الوصف: | SummaryCD44 is required for signalling of macrophage migration inhibitory factor (MIF), an anti-apoptotic pro-inflammatory cytokine. MIF is expressed and released from blood platelets, key players in the orchestration of occlusive vascular disease. Nothing is known about a role of CD44 in the regulation of platelet function. The present study thus explored whether CD44 modifies degranulation (P-selectin exposure), integrin activation, caspase activity, phosphatidylserine exposure on the platelet surface, platelet volume, Orai1 protein abundance and cytosolic Ca2+-activity ([Ca2+]i). Platelets from mice lacking CD44 (cd44-/- ) were compared to platelets from corresponding wild-type mice (cd44+/+ ). In resting platelets, P-selectin abundance, αllbβ3 inte-grin activation, caspase-3 activity and phosphatidylserine exposure were negligible in both genotypes and Orai1 protein abundance, [Ca2+]i, and volume were similar in cd44-/- and cd44+/+ platelets. Platelet degranulation and αllbβ3 integrin activation were significantly increased by thrombin (0.02 U/ml), collagen related peptide (CRP, 2 µg/ml and Ca2+-store depletion with thapsigargin (1 µM), effects more pronounced in cd44-/- than in cd44+/+ platelets. Thrombin (0.02 U/ml) increased platelet [Ca2+]i, caspase-3 activity, phosphatidylserine exposure and Orai1 surface abundance, effects again significantly stronger in cd44-/- than in cd44+/+ platelets. Thrombin further decreased forward scatter in cd44-/- and cd44+/+ platelets, an effect which tended to be again more pronounced in cd44-/- than in cd44+/+ platelets. Platelet adhesion and in vitro thrombus formation under high arterial shear rates (1,700 s-1) were significantly augmented in cd44-/- mice. In conclusion, genetic deficiency of CD44 augments activation, apoptosis and prothrombotic potential of platelets. |
| تدمد: | 2567-689X 0340-6245 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fb252d36505a5eba8b894644fc1fe290Test https://doi.org/10.1160/th14-10-0847Test |
| رقم الانضمام: | edsair.doi.dedup.....fb252d36505a5eba8b894644fc1fe290 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2567689X 03406245 |
|---|