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CD44 sensitivity of platelet activation, membrane scrambling and adhesion under high arterial shear rates
- Source :
- Thrombosis and Haemostasis. 115:99-108
- Publication Year :
- 2016
- Publisher :
- Georg Thieme Verlag KG, 2016.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 2567689X and 03406245
- Volume :
- 115
- Database :
- OpenAIRE
- Journal :
- Thrombosis and Haemostasis
- Accession number :
- edsair.doi.dedup.....fb252d36505a5eba8b894644fc1fe290