A novel role for the fibrinogen Asn-Gly-Arg (NGR) motif in platelet function.

The integrin alpha(IIIB)beta(3) on testing platelets can bind to immobilised fibrinogen resulting in platelet spreading and activation but requires activation to bind to soluble fibrinogen. alpha(IIIB)beta(3) is known to interact with the general integrin-recognition motif RGD (arginine-glycine-aspartate) as well as the fibrinogen-specific gamma-chain dodecapeptide; how: ever, 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 alpha(IIIB)beta(3). NGR-containing peptides inhibited resting platelet adhesion to fibrinogen with an IC50 of 175 mu M but failed to inhibit the adhesion of activated platelets to fibrinogen (IC50 >500 mu M). 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 alpha(IIIB)beta(3) and is responsible for triggering platelet activation.