Immobilized fibrinogen activates human platelets through glycoprotein VI.

Abstract:

:Glycoprotein VI, a major platelet activation receptor for collagen and fibrin, is considered a particularly promising, safe antithrombotic target. In this study, we show that human glycoprotein VI signals upon platelet adhesion to fibrinogen. Full spreading of human platelets on fibrinogen was abolished in platelets from glycoprotein VI- deficient patients suggesting that fibrinogen activates platelets through glycoprotein VI. While mouse platelets failed to spread on fibrinogen, human-glycoprotein VI-transgenic mouse platelets showed full spreading and increased Ca2+ signaling through the tyrosine kinase Syk. Direct binding of fibrinogen to human glycoprotein VI was shown by surface plasmon resonance and by increased adhesion to fibrinogen of human glycoprotein VI-transfected RBL-2H3 cells relative to mock-transfected cells. Blockade of human glycoprotein VI with the Fab of the monoclonal antibody 9O12 impaired platelet aggregation on preformed platelet aggregates in flowing blood independent of collagen and fibrin exposure. These results demonstrate that human glycoprotein VI binds to immobilized fibrinogen and show that this contributes to platelet spreading and platelet aggregation under flow.

journal_name

Haematologica

journal_title

Haematologica

authors

Mangin PH,Onselaer MB,Receveur N,Le Lay N,Hardy AT,Wilson C,Sanchez X,Loyau S,Dupuis A,Babar AK,Miller JL,Philippou H,Hughes CE,Herr AB,Ariëns RA,Mezzano D,Jandrot-Perrus M,Gachet C,Watson SP

doi

10.3324/haematol.2017.182972

subject

Has Abstract

pub_date

2018-05-01 00:00:00

pages

898-907

issue

5

eissn

0390-6078

issn

1592-8721

pii

haematol.2017.182972

journal_volume

103

pub_type

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