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Thromb Haemost 2016; 115(01): 99-108
DOI: 10.1160/TH14-10-0847
Cellular Haemostasis and Platelets
Schattauer GmbH Schattauer

CD44 sensitivity of platelet activation, membrane scrambling and adhesion under high arterial shear rates

Guilai Liu   *
1   Department of Physiology, University of Tübingen, Tübingen, Germany
,
Guoxing Liu   *
1   Department of Physiology, University of Tübingen, Tübingen, Germany
,
Kousi Alzoubi
1   Department of Physiology, University of Tübingen, Tübingen, Germany
,
Madhumita Chatterjee
2   Department of Cardiology and Cardiovascular Medicine, University of Tübingen, Tübingen, Germany
,
Britta Walker
1   Department of Physiology, University of Tübingen, Tübingen, Germany
2   Department of Cardiology and Cardiovascular Medicine, University of Tübingen, Tübingen, Germany
,
Patrick Münzer
1   Department of Physiology, University of Tübingen, Tübingen, Germany
2   Department of Cardiology and Cardiovascular Medicine, University of Tübingen, Tübingen, Germany
,
Dong Luo
1   Department of Physiology, University of Tübingen, Tübingen, Germany
,
Anja T. Umbach
1   Department of Physiology, University of Tübingen, Tübingen, Germany
,
Bernat Elvira
1   Department of Physiology, University of Tübingen, Tübingen, Germany
,
Hong Chen
1   Department of Physiology, University of Tübingen, Tübingen, Germany
,
Jakob Voelkl
1   Department of Physiology, University of Tübingen, Tübingen, Germany
,
Michael Föller
1   Department of Physiology, University of Tübingen, Tübingen, Germany
3   Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, UHN, Toronto, Ontario, Canada
,
Tak Z. Mak
3   Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, UHN, Toronto, Ontario, Canada
,
Oliver Borst
1   Department of Physiology, University of Tübingen, Tübingen, Germany
2   Department of Cardiology and Cardiovascular Medicine, University of Tübingen, Tübingen, Germany
,
Meinrad Gawaz
2   Department of Cardiology and Cardiovascular Medicine, University of Tübingen, Tübingen, Germany
,
Florian Lang
1   Department of Physiology, University of Tübingen, Tübingen, Germany
› Author Affiliations Financial support:This study was supported by the Deutsche Forschungsgemeinschaft – Klinische Forschergruppe [DFG-KFO 274] ‘Platelets–Molecular Mechanisms and Translational Implications’, fortüne (2312–0–0) and DFG (BO 3786/1–1) research grants as well as the Tuebingen Platelet Investigative Consortium (TuePIC).
Further Information

Publication History

Received: 12 October 2014

Accepted after major revision: 26 July 2015

Publication Date:
22 November 2017 (online)

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Summary

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, 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.

Keywords

CD44 - platelet activation - cytosolic Ca2+ concentration - phosphatidylserine translocation - thrombus formation

* Both authors contributed equally and thus share first authorship.


 

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