Fibrin activates GPVI in human and mouse platelets

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Fibrin activates GPVI in human and mouse platelets. / Alshehri, Osama M; Hughes, Craig E; Montague, Samantha; Watson, Stephanie K; Frampton, Jonathan; Bender, Markus; Watson, Steve P.

In: Blood, Vol. 126, No. 13, 24.09.2015, p. 1601-1608.

Research output: Contribution to journalArticlepeer-review

Harvard

Alshehri, OM, Hughes, CE, Montague, S, Watson, SK, Frampton, J, Bender, M & Watson, SP 2015, 'Fibrin activates GPVI in human and mouse platelets', Blood, vol. 126, no. 13, pp. 1601-1608. https://doi.org/10.1182/blood-2015-04-641654

APA

Vancouver

Alshehri OM, Hughes CE, Montague S, Watson SK, Frampton J, Bender M et al. Fibrin activates GPVI in human and mouse platelets. Blood. 2015 Sep 24;126(13):1601-1608. https://doi.org/10.1182/blood-2015-04-641654

Author

Alshehri, Osama M ; Hughes, Craig E ; Montague, Samantha ; Watson, Stephanie K ; Frampton, Jonathan ; Bender, Markus ; Watson, Steve P. / Fibrin activates GPVI in human and mouse platelets. In: Blood. 2015 ; Vol. 126, No. 13. pp. 1601-1608.

Bibtex

@article{1dae8db0ca2646348cce79c083ffce54,
title = "Fibrin activates GPVI in human and mouse platelets",
abstract = "The glycoprotein VI (GPVI)-Fc receptor γ (FcRγ) chain is the major platelet signaling receptor for collagen. Paradoxically, in a FeCl3 injury model, occlusion, but not initiation of thrombus formation, is delayed in GPVI-deficient and GPVI-depleted mice. In this study, we demonstrate that GPVI is a receptor for fibrin and speculate that this contributes to development of an occlusive thrombus. We observed a marked increase in tyrosine phosphorylation, including the FcRγ chain and Syk, in human and mouse platelets induced by thrombin in the presence of fibrinogen and the αIIbβ3 blocker eptifibatide. This was not seen in platelets stimulated by a protease activated receptor (PAR)-4 peptide, which is unable to generate fibrin from fibrinogen. The pattern of tyrosine phosphorylation was similar to that induced by activation of GPVI. Consistent with this, thrombin did not induce tyrosine phosphorylation of Syk and the FcRγ chain in GPVI-deficient mouse platelets. Mouse platelets underwent full spreading on fibrin but not fibrinogen, which was blocked in the presence of a Src kinase inhibitor or in the absence of GPVI. Spreading on fibrin was associated with phosphatidylserine exposure (procoagulant activity), and this too was blocked in GPVI-deficient platelets. The ectodomain of GPVI was shown to bind to immobilized monomeric and polymerized fibrin. A marked increase in embolization was seen following FeCl3 injury in GPVI-deficient mice, likely contributing to the delay in occlusion in this model. These results demonstrate that GPVI is a receptor for fibrin and provide evidence that this interaction contributes to thrombus growth and stability.",
author = "Alshehri, {Osama M} and Hughes, {Craig E} and Samantha Montague and Watson, {Stephanie K} and Jonathan Frampton and Markus Bender and Watson, {Steve P}",
note = "{\textcopyright} 2015 by The American Society of Hematology.",
year = "2015",
month = sep,
day = "24",
doi = "10.1182/blood-2015-04-641654",
language = "English",
volume = "126",
pages = "1601--1608",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "13",

}

RIS

TY - JOUR

T1 - Fibrin activates GPVI in human and mouse platelets

AU - Alshehri, Osama M

AU - Hughes, Craig E

AU - Montague, Samantha

AU - Watson, Stephanie K

AU - Frampton, Jonathan

AU - Bender, Markus

AU - Watson, Steve P

N1 - © 2015 by The American Society of Hematology.

PY - 2015/9/24

Y1 - 2015/9/24

N2 - The glycoprotein VI (GPVI)-Fc receptor γ (FcRγ) chain is the major platelet signaling receptor for collagen. Paradoxically, in a FeCl3 injury model, occlusion, but not initiation of thrombus formation, is delayed in GPVI-deficient and GPVI-depleted mice. In this study, we demonstrate that GPVI is a receptor for fibrin and speculate that this contributes to development of an occlusive thrombus. We observed a marked increase in tyrosine phosphorylation, including the FcRγ chain and Syk, in human and mouse platelets induced by thrombin in the presence of fibrinogen and the αIIbβ3 blocker eptifibatide. This was not seen in platelets stimulated by a protease activated receptor (PAR)-4 peptide, which is unable to generate fibrin from fibrinogen. The pattern of tyrosine phosphorylation was similar to that induced by activation of GPVI. Consistent with this, thrombin did not induce tyrosine phosphorylation of Syk and the FcRγ chain in GPVI-deficient mouse platelets. Mouse platelets underwent full spreading on fibrin but not fibrinogen, which was blocked in the presence of a Src kinase inhibitor or in the absence of GPVI. Spreading on fibrin was associated with phosphatidylserine exposure (procoagulant activity), and this too was blocked in GPVI-deficient platelets. The ectodomain of GPVI was shown to bind to immobilized monomeric and polymerized fibrin. A marked increase in embolization was seen following FeCl3 injury in GPVI-deficient mice, likely contributing to the delay in occlusion in this model. These results demonstrate that GPVI is a receptor for fibrin and provide evidence that this interaction contributes to thrombus growth and stability.

AB - The glycoprotein VI (GPVI)-Fc receptor γ (FcRγ) chain is the major platelet signaling receptor for collagen. Paradoxically, in a FeCl3 injury model, occlusion, but not initiation of thrombus formation, is delayed in GPVI-deficient and GPVI-depleted mice. In this study, we demonstrate that GPVI is a receptor for fibrin and speculate that this contributes to development of an occlusive thrombus. We observed a marked increase in tyrosine phosphorylation, including the FcRγ chain and Syk, in human and mouse platelets induced by thrombin in the presence of fibrinogen and the αIIbβ3 blocker eptifibatide. This was not seen in platelets stimulated by a protease activated receptor (PAR)-4 peptide, which is unable to generate fibrin from fibrinogen. The pattern of tyrosine phosphorylation was similar to that induced by activation of GPVI. Consistent with this, thrombin did not induce tyrosine phosphorylation of Syk and the FcRγ chain in GPVI-deficient mouse platelets. Mouse platelets underwent full spreading on fibrin but not fibrinogen, which was blocked in the presence of a Src kinase inhibitor or in the absence of GPVI. Spreading on fibrin was associated with phosphatidylserine exposure (procoagulant activity), and this too was blocked in GPVI-deficient platelets. The ectodomain of GPVI was shown to bind to immobilized monomeric and polymerized fibrin. A marked increase in embolization was seen following FeCl3 injury in GPVI-deficient mice, likely contributing to the delay in occlusion in this model. These results demonstrate that GPVI is a receptor for fibrin and provide evidence that this interaction contributes to thrombus growth and stability.

U2 - 10.1182/blood-2015-04-641654

DO - 10.1182/blood-2015-04-641654

M3 - Article

C2 - 26282541

VL - 126

SP - 1601

EP - 1608

JO - Blood

JF - Blood

SN - 0006-4971

IS - 13

ER -