The Platelet Integrin αIIbß3 Differentially Interacts with Fibrin Versus Fibrinogen.
J Biol Chem
; 291(15): 7858-67, 2016 Apr 08.
Article
em En
| MEDLINE
| ID: mdl-26867579
ABSTRACT
Fibrinogen binding to the integrin αIIbß3 mediates platelet aggregation and spreading on fibrinogen-coated surfaces. However,in vivoαIIbß3 activation and fibrinogen conversion to fibrin occur simultaneously, although the relative contributions of fibrinogenversusfibrin to αIIbß3-mediated platelet functions are unknown. Here, we compared the interaction of αIIbß3 with fibrin and fibrinogen to explore their differential effects. A microscopic bead coated with fibrinogen or monomeric fibrin produced by treating the immobilized fibrinogen with thrombin was captured by a laser beam and repeatedly brought into contact with surface-attached purified αIIbß3. When αIIbß3-ligand complexes were detected, the rupture forces were measured and displayed as force histograms. Monomeric fibrin displayed a higher probability of interacting with αIIbß3 and a greater binding strength. αIIbß3-fibrin interactions were also less sensitive to inhibition by abciximab and eptifibatide. Both fibrinogen- and fibrin-αIIbß3 interactions were partially inhibited by RGD peptides, suggesting the existence of common RGD-containing binding motifs. This assumption was supported using the fibrin variants αD97E or αD574E with mutated RGD motifs. Fibrin made from a fibrinogen γ'/γ' variant lacking the γC αIIbß3-binding motif was more reactive with αIIbß3 than the parent fibrinogen. These results demonstrate that fibrin is more reactive with αIIbß3 than fibrinogen. Fibrin is also less sensitive to αIIbß3 inhibitors, suggesting that fibrin and fibrinogen have distinct binding requirements. In particular, the maintenance of αIIbß3 binding activity in the absence of the γC-dodecapeptide and the α-chain RGD sequences suggests that the αIIbß3-binding sites in fibrin are not confined to its known γ-chain and RGD motifs.
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Base de dados:
MEDLINE
Assunto principal:
Plaquetas
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Fibrinogênio
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Fibrina
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Complexo Glicoproteico GPIIb-IIIa de Plaquetas
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article