| First Author | Chen W | Year | 2017 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 37 |
| Issue | 12 | Pages | 2271-2279 |
| PubMed ID | 29097365 | Mgi Jnum | J:269172 |
| Mgi Id | MGI:6272072 | Doi | 10.1161/ATVBAHA.117.310062 |
| Citation | Chen W, et al. (2017) Refrigeration-Induced Binding of von Willebrand Factor Facilitates Fast Clearance of Refrigerated Platelets. Arterioscler Thromb Vasc Biol 37(12):2271-2279 |
| abstractText | OBJECTIVE: Apheresis platelets for transfusion treatment are currently stored at room temperature because after refrigeration platelets are rapidly cleared on transfusion. In this study, the role of von Willebrand factor (VWF) in the clearance of refrigerated platelets is addressed. APPROACH AND RESULTS: Human and murine platelets were refrigerated in gas-permeable bags at 4 degrees C for 24 hours. VWF binding, platelet signaling events, and platelet post-transfusion recovery and survival were measured. After refrigeration, the binding of plasma VWF to platelets was drastically increased, confirming earlier studies. The binding was blocked by peptide OS1 that bound specifically to platelet glycoprotein (GP)Ibalpha and was absent in VWF(-)(/)(-) plasma. Although surface expression of GPIbalpha was reduced after refrigeration, refrigeration-induced VWF binding under physiological shear induced unfolding of the GPIbalpha mechanosensory domain on the platelet, as evidenced by increased exposure of a linear epitope therein. Refrigeration and shear treatment also induced small elevation of intracellular Ca(2+), phosphatidylserine exposure, and desialylation of platelets, which were absent in VWF(-/-) platelets or inhibited by OS1, which is a monomeric 11-residue peptide (CTERMALHNLC). Furthermore, refrigerated VWF(-/-) platelets displayed increased post-transfusion recovery and survival than wild-type ones. Similarly, adding OS1 to transgenic murine platelets expressing only human GPIbalpha during refrigeration improved their post-transfusion recovery and survival. CONCLUSIONS: Refrigeration-induced binding of VWF to platelets facilitates their rapid clearance by inducing GPIbalpha-mediated signaling. Our results suggest that inhibition of the VWF-GPIbalpha interaction may be a potential strategy to enable refrigeration of platelets for transfusion treatment. |
