| First Author | Kaplan ZS | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 7835 | PubMed ID | 26204458 |
| Mgi Jnum | J:224445 | Mgi Id | MGI:5662303 |
| Doi | 10.1038/ncomms8835 | Citation | Kaplan ZS, et al. (2015) Thrombin-dependent intravascular leukocyte trafficking regulated by fibrin and the platelet receptors GPIb and PAR4. Nat Commun 6:7835 |
| abstractText | Thrombin is a central regulator of leukocyte recruitment and inflammation at sites of vascular injury, a function thought to involve primarily endothelial PAR cleavage. Here we demonstrate the existence of a distinct leukocyte-trafficking mechanism regulated by components of the haemostatic system, including platelet PAR4, GPIbalpha and fibrin. Utilizing a mouse endothelial injury model we show that thrombin cleavage of platelet PAR4 promotes leukocyte recruitment to sites of vascular injury. This process is negatively regulated by GPIbalpha, as seen in mice with abrogated thrombin-platelet GPIbalpha binding (hGPIbalpha(D277N)). In addition, we demonstrate that fibrin limits leukocyte trafficking by forming a physical barrier to intravascular leukocyte migration. These studies demonstrate a distinct 'checkpoint' mechanism of leukocyte trafficking involving balanced thrombin interactions with PAR4, GPIbalpha and fibrin. Dysregulation of this checkpoint mechanism is likely to contribute to the development of thromboinflammatory disorders. |
