Glutathione regulates integrin αIIbβ3-mediated cell adhesion under flow conditions

Chalmette Ball; K. Vinod Vijayan; Trung Nguyen; Kim Anthony; Paul F. Bray; David W. Essex; Jing-fei Dong

doi:10.1160/TH08-02-0095

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 100(05): 857-863
DOI: 10.1160/TH08-02-0095

Platelets and Blood Cells

Schattauer GmbH

Glutathione regulates integrin α_IIbβ₃-mediated cell adhesion under flow conditions

Chalmette Ball

¹Thrombosis Research Section, Department of Medicine

,

K. Vinod Vijayan

¹Thrombosis Research Section, Department of Medicine

,

Trung Nguyen

²Critical Care Section, Department of Pediatrics, Baylor Collage of Medicine, Houston, Texas, USA

,

Kim Anthony

¹Thrombosis Research Section, Department of Medicine

,

Paul F. Bray

³Section of Hematology, Department of Medicine, Thomas Jefferson University, School of Medicine, Philadelphia, Pennsylvania, USA

,

David W. Essex

⁴Section of Hematology-Oncology, Department of Medicine, University of Texas, Health Science Center at San Antonio, San Antonio, Texas, USA

,

Jing-fei Dong

¹Thrombosis Research Section, Department of Medicine

› Author Affiliations

Abstract

Summary

The platelet integrin α_IIbβ₃ mediates the final step of platelet aggregation that requires pre-activation through an inside-out signal initiated by agonists. Experiments conducted under static conditions using platelet-rich plasma show that platelet activation and adhesion activity of α_IIbβ₃ are regulated by glutathione (GSH-GSSG) redox potential.However,it remains unclear as to whether GSH-GSSG exerts its regulatory role in platelets by direct targeting of α_IIbβ₃ or intracellular signals that activate the integrin. A role of fluid shear stress is also not known. We examined the effects of GSH-GSSG on the adhesion of CHO cells expressing two HPA variants of human α_IIbβ₃ to the immobilized fibrinogen and von Willebrand factor (VWF) under flow conditions. GSH-GSSG dose-dependently reduced the number of adherent cells to fibrinogen and VWF under 2.5 dyn/cm² of shear stress, a physical force calculated to be 110 dyne on platelets. GSH treatment also abolished the hyperadhesion activity of cells expressing the Pro33 variant of α_IIbβ₃.The inhibition was also observed with washed platelets. The data differ from the early observation that GSH enhanced platelet aggregation induced by sub-threshold concentrations of platelet agonists. The results suggest that GSH may have distinct effects on agonist-induced α_IIbβ₃ activation and on the α_IIbβ₃-fibrinogen or α_IIbβ₃-VWF bonds when exposed to fluid shear stress. They further suggest that the HPA phenotype may be redox-regulated.

Keywords

Adhesion receptors - platelet glycoproteins - rheology / mechanical stimuli - fibrinogen / fibrin - von Willebrand factor

Full Text

References

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