Thrombin-dependent intravascular leukocyte trafficking regulated by fibrin and the platelet receptors GPIb and PAR4

• DOI: 10.1038/ncomms8835
• Publication Date: 2015-07-23T12:33:23Z
• Authors: Zane S. Kaplan; Alessandro Zarpellon; Imala Alwis; Yuping Yuan; James McFadyen; Mehran Ghasemzadeh; Simone M. Schoenw...; Zaverio M. Ruggeri; Shaun P. Jackson
• Keywords: Leukocyte Trafficking; Cleavage (geology)

Thrombin is a central regulator of leukocyte recruitment and inflammation at sites vascular injury, function thought to involve primarily endothelial PAR cleavage. Here we demonstrate the existence distinct leukocyte-trafficking mechanism regulated by components haemostatic system, including platelet PAR4, GPIbα fibrin. Utilizing mouse injury model show that thrombin cleavage PAR4 promotes injury. This process negatively GPIbα, as seen in mice with abrogated thrombin-platelet binding (hGPIbαD277N). In addition, fibrin limits trafficking forming physical barrier intravascular migration. These studies ‘checkpoint’ involving balanced interactions Dysregulation this checkpoint likely contribute development thromboinflammatory disorders. key proinflammatory protease regulating authors proteins plays major role process.