Peer Reviewed

1

Document Type

Article

Publication Date

20-11-2014

Keywords

Platelets, Fibrinogen, Platelet Activation, GPIIb-IIIa

Funder/Sponsor

Health Research Board, Irish Research Council, Science Foundation Ireland

Comments

This article is not an exact copy of the original published article in Thrombosis and Haemostasis. The definitive publisher-authenticated version of Moriarty R, McManus CA, Lambert M, Tiley T, Devocelle M, Brennan M, Kerrigan W, Cox D. A novel role for the fibrinogen Asn-Gly-Arg (NGR) motif in platelet function. Thrombosis and Haemostasis. 2014;113(2) is available online at: http://th.schattauer.de/en/contents/archive/issue/special/manuscript/23713.html

Abstract

The integrin αIIbβ3 on resting platelets can bind to immobilised fibrinogen resulting in platelet spreading and activation but requires activation to bind to soluble fibrinogen. αIIbβ3 is known to interact with the general integrin-recognition motif RGD (arginine-glycine-aspartate) as well as the fibrinogen-specific γ-chain dodecapeptide; however, it is not known how fibrinogen binding triggers platelet activation. NGR (asparagine-glycine-arginine) is another integrin-recognition sequence present in fibrinogen and this study aims to determine if it plays a role in the interaction between fibrinogen and αIIbβ3. NGR-containing peptides inhibited resting platelet adhesion to fibrinogen with an IC50 of 175 µM but failed to inhibit the adhesion of activated platelets to fibrinogen (IC50> 500 µM). Resting platelet adhesion to mutant fibrinogens lacking the NGR sequences was reduced compared to normal fibrinogen under both static and shear conditions (200 s⁻¹). However, pre-activated platelets were able to fully spread on all types of fibrinogen. Thus, the NGR motif in fibrinogen is the site that is primarily responsible for the interaction with resting αIIbβ3 and is responsible for triggering platelet activation.

Disciplines

Life Sciences | Medicine and Health Sciences

Citation

Moriarty R, McManus CA, Lambert M, Tiley T, Devocelle M, Brennan M, Kerrigan W, Cox D. A novel role for the fibrinogen Asn-Gly-Arg (NGR) motif in platelet function. Thrombosis and Haemostasis. 2014;113(2) [Epub ahead of print].

PubMed ID

25413489

DOI Link

10.1160/TH14-04-0366

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