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Thromb Haemost 2008; 100(05): 857-863
DOI: 10.1160/TH08-02-0095
Platelets and Blood Cells
Schattauer GmbH

Glutathione regulates integrin αIIbβ3-mediated cell adhesion under flow conditions

Chalmette Ball
1   Thrombosis Research Section, Department of Medicine
,
K. Vinod Vijayan
1   Thrombosis Research Section, Department of Medicine
,
Trung Nguyen
2   Critical Care Section, Department of Pediatrics, Baylor Collage of Medicine, Houston, Texas, USA
,
Kim Anthony
1   Thrombosis Research Section, Department of Medicine
,
Paul F. Bray
3   Section of Hematology, Department of Medicine, Thomas Jefferson University, School of Medicine, Philadelphia, Pennsylvania, USA
,
David W. Essex
4   Section of Hematology-Oncology, Department of Medicine, University of Texas, Health Science Center at San Antonio, San Antonio, Texas, USA
,
Jing-fei Dong
1   Thrombosis Research Section, Department of Medicine
› Author AffiliationsFinancial support: This work was supported by the NIH grants HL71895 (J.F.D), HL081613 (K.V.V), HL65229 (P.F.B) and a VA Merit Grant (DWE).
Further Information

Publication History

Received 19 February 2008

Accepted after major revision 24 August 2008

Publication Date:
22 November 2017 (online)

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Summary

The platelet integrin αIIbβ3 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 αIIbβ3 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 αIIbβ3 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 αIIbβ3 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 αIIbβ3.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 αIIbβ3 activation and on the αIIbβ3-fibrinogen or αIIbβ3-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
 

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