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Blood. 2013 Oct 10;122(15):2723-31. doi: 10.1182/blood-2013-06-508721. Epub 2013 Sep 4.

β1 integrin-mediated signals are required for platelet granule secretion and hemostasis in mouse.

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1
Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany;

Abstract

Integrins are critical for platelet adhesion and aggregation during arterial thrombosis and hemostasis. Although the platelet-specific αIIbβ3 integrin is known to be crucial for these processes, the in vivo role of β1 integrins is a matter of debate. Here we demonstrate that mice expressing reduced levels of β1 integrins or an activation-deficient β1 integrin show strongly reduced platelet adhesion to collagen in vitro and in a carotis ligation model in vivo. Interestingly, hypomorphic mice expressing only 3% of β1 integrins on platelets show normal bleeding times despite reduced platelet adhesion. The residual 3% of β1 integrins are able to trigger intracellular signals driving Rac-1-dependent granule release required for platelet aggregation and hemostasis. Our findings support a model, in which platelet β1 integrins serve as an important signaling receptor rather than an adhesion receptor in vivo and therefore promote β1 integrins as a promising and so far clinically unemployed antithrombotic target.

PMID:
24004668
DOI:
10.1182/blood-2013-06-508721
[Indexed for MEDLINE]
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