The effects of 22°C and 4°C storage of platelets on vascular endothelial integrity and function

BACKGROUNDAlthough a majority of the studies conducted to date on platelet (PLT) storage have been focused on PLT hemostatic function, the effects of 4 degrees C PLTs on regulation of endothelial barrier permeability are still not known. In this study, we compared the effects of room temperature (22 degrees C) stored and (4 degrees C) stored PLTs on the regulation of vascular endothelial cell (EC) permeability in vitro and in vivo. STUDY DESIGN AND METHODSDay 1, Day 5, and Day 7 leukoreduced apheresis PLTs stored at 4 or 22 degrees C were studied in vitro and in vivo. In vitro, PLT effects on EC permeability and barrier function, adhesion, and impedance aggregometry were investigated. In vivo, using a mouse model of vascular leak, attenuation of vascular leak and circulating PLT numbers were measured. RESULTSTreatment of EC monolayers with Day 5 or Day 7 PLTs, stored at both 22 degrees C and 4 degrees C, resulted in similar decreases in EC permeability on average. However, analysis of individual samples revealed significant variation that was donor dependent. Additional in vitro measurements revealed a decrease in inflammatory mediators, nonspecific PLT-endothelial aggregation and attenuated loss of aggregation over time to TRAP, ASPI, ADP, and collagen with 4 degrees C storage. In mice, while 22 degrees C and 4 degrees C PLTs both demonstrated significant protection against vascular endothelial growth factor A (VEGF-A)-induced vascular leak 22 degrees C PLTs exhibited increased protection compared to 4 degrees C PLTs. Systemic circulating levels of 4 degrees C PLTs were decreased compared to 22 degrees C PLTs. CONCLUSIONSIn vitro, 4 degrees C-stored PLTs exhibit a greater capacity to inhibit EC permeability than 22 degrees C-stored PLTs. In vivo, 22 degrees C PLTs provide superior control of vascular leak induced by VEGF-A. This discrepancy may be due to increased clearance of 4 degrees C PLTs from the systemic circulation.