First Author | Petzold T | Year | 2013 |
Journal | Blood | Volume | 122 |
Issue | 15 | Pages | 2723-31 |
PubMed ID | 24004668 | Mgi Jnum | J:203825 |
Mgi Id | MGI:5528784 | Doi | 10.1182/blood-2013-06-508721 |
Citation | Petzold T, et al. (2013) beta1 integrin-mediated signals are required for platelet granule secretion and hemostasis in mouse. Blood 122(15):2723-31 |
abstractText | Integrins are critical for platelet adhesion and aggregation during arterial thrombosis and hemostasis. Although the platelet-specific alphaIIbbeta3 integrin is known to be crucial for these processes, the in vivo role of beta1 integrins is a matter of debate. Here we demonstrate that mice expressing reduced levels of beta1 integrins or an activation-deficient beta1 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 beta1 integrins on platelets show normal bleeding times despite reduced platelet adhesion. The residual 3% of beta1 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 beta1 integrins serve as an important signaling receptor rather than an adhesion receptor in vivo and therefore promote beta1 integrins as a promising and so far clinically unemployed antithrombotic target. |