Differential integrin activity mediated by platelet collagen receptor engagement under flow conditions.
Thromb Haemost
; 117(8): 1588-1600, 2017 07 26.
Article
em En
| MEDLINE
| ID: mdl-28536721
ABSTRACT
The platelet receptors glycoprotein (Gp)VI, integrin α2ß1 and GpIb/V/IX mediate platelet adhesion and activation during thrombogenesis. Increases of intracellular Ca2+ ([Ca2+]i) are key signals during platelet activation; however, their relative importance in coupling different collagen receptors to functional responses under shear conditions remains unclear. To study shear-dependent, receptor-specific platelet responses, we used collagen or combinations of receptor-specific collagen-mimetic peptides as substrates for platelet adhesion and activation in whole human blood under arterial flow conditions and compared real-time and endpoint parameters of thrombus formation alongside [Ca2+]i measurements using confocal imaging. All three collagen receptors coupled to [Ca2+]i signals, but these varied in amplitude and temporal pattern alongside variable integrin activation. GpVI engagement produced large, sustained [Ca2+]i signals leading to real-time increases in integrins α2ß1- and αIIbß3-mediated platelet adhesion. αIIbß3-dependent platelet aggregation was dependent on P2Y12 signalling. Co-engagement of α2ß1 and GpIb/V/IX generated transient [Ca2+]i spikes and low amplitude [Ca2+]i responses that potentiated GpVI-dependent [Ca2+]i signalling. Therefore α2ß1, GpIb/V/IX and GpVI synergise to generate [Ca2+]i signals that regulate platelet behaviour and thrombus formation. Antagonism of secondary signalling pathways reveals distinct, separate roles for αIIbß3 in stable platelet adhesion and aggregation.
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Base de dados:
MEDLINE
Assunto principal:
Plaquetas
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Glicoproteínas da Membrana de Plaquetas
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Ativação Plaquetária
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Hemorreologia
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Complexo Glicoproteico GPIIb-IIIa de Plaquetas
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Sinalização do Cálcio
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Integrina alfa2beta1
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article