Contact- and agonist-regulated microvesiculation of human platelets

Yanjun Zhang; Xiao Liu; Li Liu; Ana-Maria Zaske; Zhou Zhou; Yuanyuan Fu; Xi Yang; Jodie L. Conyers; Min Li; Jing-fei Dong; Jianning Zhang

doi:10.1160/TH12-11-0853

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2013; 110(02): 331-399
DOI: 10.1160/TH12-11-0853

Platelets and Blood Cells

Schattauer GmbH

Contact- and agonist-regulated microvesiculation of human platelets

Yanjun Zhang

¹Tianjin Neurological Institute, Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China

²Chinese National Academy of Nanotechnology & Engineering, Tianjin, China

,

Xiao Liu

²Chinese National Academy of Nanotechnology & Engineering, Tianjin, China

,

Li Liu

¹Tianjin Neurological Institute, Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China

,

Ana-Maria Zaske

³Division of Cardiology, Department of Internal Medicine, the University of Texas Houston Health Science Center at Houston, Texas, USA

,

Zhou Zhou

⁴Puget Sound Blood Center, Seattle, Washington, USA

⁵Department of Laboratory Medicine, Fuwai Cardiovascular Hospital, the Chinese Academy of Sciences, Beijing, China

,

Yuanyuan Fu

⁴Puget Sound Blood Center, Seattle, Washington, USA

⁵Department of Laboratory Medicine, Fuwai Cardiovascular Hospital, the Chinese Academy of Sciences, Beijing, China

,

Xi Yang

²Chinese National Academy of Nanotechnology & Engineering, Tianjin, China

,

Jodie L. Conyers

³Division of Cardiology, Department of Internal Medicine, the University of Texas Houston Health Science Center at Houston, Texas, USA

,

Min Li

⁶Pathology Institute, Lanzhou University, School of Basic Medical Sciences, Lanzhou, China

,

Jing-fei Dong

⁴Puget Sound Blood Center, Seattle, Washington, USA

⁷Division of Hematology, Department of Medicine, University of Washington, School of Medicine, Seattle, Washington, USA

,

Jianning Zhang

¹Tianjin Neurological Institute, Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China

› Author Affiliations

Abstract

Summary

After exposure to an agonist, platelets are activated and become aggregated. They also shed membrane microparticles that participate in the pathogenesis of thrombosis, hyper-coagulation and inflammation. However, microvesiculation can potentially disrupt the integrity of platelet aggregation by shedding the membrane receptors and phosphatidylserine critical for forming and stabilising a platelet clot. We tested the hypothesis that adhesion and microvesiculation are functions of different subsets of platelets at the time of haemostasis by real-time monitoring of agonist-induced morphological changes and microvesiculation of human platelets. We identified two types of platelets that are adherent to fibrinogen: a high density bubble shape (HDBS) and low-density spread shape (LDSS). Adenosine diphosphate (ADP) predominantly induced HDBS platelets to vesiculate, whereas LDSS platelets were highly resistant to such vesiculation. Thrombin-receptor activating peptide (TRAP) stabilised platelets against microvesiculation by promoting a rapid HDBS-to-LDSS morphological transition. These activities of ADP and TRAP were reversed for platelets in suspension, independent of an engagement integrin αIIbβ 3. As the result of membrane contact, LDSS platelets inhibited the microvesiculation of HDBS platelets in response to ADP. Aspirin and clopidogrel inhibited ADP-induced microvesiculation through different mechanisms. These results suggest that platelet aggregation and microvesiculation occur in different subsets of platelets and are differently regulated by agonists, platelet-platelets and platelet-fibrinogen interactions.

Keywords

Platelets - microvesiculation - contact inhibition - anti-platelet drugs

Full Text

References

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