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- Publisher Website: 10.1160/TH14-10-0847
- Scopus: eid_2-s2.0-84951287078
- PMID: 26355696
- WOS: WOS:000367265000012
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Article: CD44 sensitivity of platelet activation, membrane scrambling and adhesion under high arterial shear rates
Title | CD44 sensitivity of platelet activation, membrane scrambling and adhesion under high arterial shear rates |
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Authors | |
Keywords | Thrombus formation Platelet activation CD44 Cytosolic Ca concentration 2+ Phosphatidylserine translocation |
Issue Date | 2016 |
Citation | Thrombosis and Haemostasis, 2016, v. 115, n. 1, p. 99-108 How to Cite? |
Abstract | © Schattauer 2016. CD44 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, αIIbβ3 integrin 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 αIIbβ3 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. |
Persistent Identifier | http://hdl.handle.net/10722/292921 |
ISSN | 2023 Impact Factor: 5.0 2023 SCImago Journal Rankings: 1.248 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Liu, Guilai | - |
dc.contributor.author | Liu, Guoxing | - |
dc.contributor.author | Alzoubi, Kousi | - |
dc.contributor.author | Chatterjee, Madhumita | - |
dc.contributor.author | Walker, Britta | - |
dc.contributor.author | Münzer, Patrick | - |
dc.contributor.author | Luo, Dong | - |
dc.contributor.author | Umbach, Anja T. | - |
dc.contributor.author | Elvira, Bernat | - |
dc.contributor.author | Chen, Hong | - |
dc.contributor.author | Voelkl, Jakob | - |
dc.contributor.author | Föller, Michael | - |
dc.contributor.author | Mak, Tak W. | - |
dc.contributor.author | Borst, Oliver | - |
dc.contributor.author | Gawaz, Meinrad | - |
dc.contributor.author | Lang, Florian | - |
dc.date.accessioned | 2020-11-17T14:57:30Z | - |
dc.date.available | 2020-11-17T14:57:30Z | - |
dc.date.issued | 2016 | - |
dc.identifier.citation | Thrombosis and Haemostasis, 2016, v. 115, n. 1, p. 99-108 | - |
dc.identifier.issn | 0340-6245 | - |
dc.identifier.uri | http://hdl.handle.net/10722/292921 | - |
dc.description.abstract | © Schattauer 2016. CD44 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, αIIbβ3 integrin 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 αIIbβ3 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. | - |
dc.language | eng | - |
dc.relation.ispartof | Thrombosis and Haemostasis | - |
dc.subject | Thrombus formation | - |
dc.subject | Platelet activation | - |
dc.subject | CD44 | - |
dc.subject | Cytosolic Ca concentration 2+ | - |
dc.subject | Phosphatidylserine translocation | - |
dc.title | CD44 sensitivity of platelet activation, membrane scrambling and adhesion under high arterial shear rates | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1160/TH14-10-0847 | - |
dc.identifier.pmid | 26355696 | - |
dc.identifier.scopus | eid_2-s2.0-84951287078 | - |
dc.identifier.volume | 115 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | 99 | - |
dc.identifier.epage | 108 | - |
dc.identifier.isi | WOS:000367265000012 | - |
dc.identifier.issnl | 0340-6245 | - |