| First Author | Prakash P | Year | 2017 |
| Journal | J Thromb Haemost | Volume | 15 |
| Issue | 2 | Pages | 388-394 |
| PubMed ID | 27943541 | Mgi Jnum | J:339789 |
| Mgi Id | MGI:6880810 | Doi | 10.1111/jth.13586 |
| Citation | Prakash P, et al. (2017) P-selectin can promote thrombus propagation independently of both von Willebrand factor and thrombospondin-1 in mice. J Thromb Haemost 15(2):388-394 |
| abstractText | Essentials The main receptor for platelet glycoprotein (GP) Ibalpha is von Willebrand factor (VWF). P-selectin and thrombospondin-1 (TSP1) have been suggested as counter receptors for GPIbalpha. In a laser injury model, P-selectin promotes thrombus propagation independently of VWF and TSP1. In a laser injury model, thrombus persists in interleukin-4 receptor alpha/GPIbalpha-transgenic mice. SUMMARY: Background P-selectin and thrombospondin-1 (TSP1) have been suggested as counter ligands that may mediate GPIbalpha-dependent thrombus growth independently of von Willebrand factor (VWF) in vitro. However, residual thrombus formation still persists in Vwf (-/-) Tsp1(-/-) mice, suggesting existence of other mechanisms that modulate thrombus propagation. Objective We determined whether P-selectin modulates thrombus propagation in injured arterioles independently of TSP1 and VWF. Methods CD-62P blocking antibody in Vwf (-/-) Tsp1(-/-) mice was used to inhibit P-selectin. We determined thrombus growth kinetics in two models of thrombosis: FeCl3 injury-induced and laser injury-induced thrombosis. Results In a 10% FeCl3 injury-induced thrombosis model, the initial platelet adhesion, time to form first thrombus, and non-occlusive residual thrombus growth kinetics were comparable between P-selectin-blocking antibody-treated Vwf (-/-) Tsp1(-/-) mice and control IgG-treated Vwf (-/-) Tsp1(-/-) mice. On the other hand, in a laser injury-induced thrombosis model, residual thrombus growth kinetics were significantly decreased in P-selectin-blocking antibody-treated Vwf (-/-) Tsp1(-/-) mice vs. control IgG-treated Vwf (-/-) Tsp1(-/-) mice. Because P-selectin has been suggested as a counter ligand for platelet GPIbalpha, we determined the role of GPIbalpha in a laser injury-induced thrombosis model. Surprisingly, in a laser injury model, unlike in a FeCl3 injury model, thrombus formation was not completely inhibited in IL4Ralpha/GPIbalpha-tg mice. Residual thrombus growth kinetics were comparable between P-selectin-blocking antibody-treated IL4Ralpha/GPIbalpha-tg mice and control IgG-treated IL4Ralpha/GPIbalpha-tg mice. Comparison of slopes over time showed that residual thrombus growth kinetics were comparable in P-selectin-blocking antibody-treated Vwf (-/-) Tsp1(-/-) and control IgG-treated IL4Ralpha/GPIbalpha-tg mice Conclusion In a laser injury-induced thrombosis model, P-selectin modulates thrombus propagation independently of VWF and TSP1. |
