title: The effects of 22°C and 4°C storage of platelets on vascular endothelial integrity and function.
abstract: BACKGROUND
  Although a majority of the studies conducted to date on platelet (PLT) storage have been focused on PLT hemostatic function, the effects of 4°C PLTs on regulation of endothelial barrier permeability are still not known. In this study, we compared the effects of room temperature (22°C) stored and (4°C) stored PLTs on the regulation of vascular endothelial cell (EC) permeability in vitro and in vivo.
  
  
  METHODS
  Day 1, Day 5, and Day 7 leukoreduced apheresis PLTs stored at 4 or 22°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.
  
  
  RESULTS
  Treatment of EC monolayers with Day 5 or Day 7 PLTs, stored at both 22°C and 4°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°C storage. In mice, while 22°C and 4°C PLTs both demonstrated significant protection against vascular endothelial growth factor A (VEGF-A)-induced vascular leak 22°C PLTs exhibited increased protection compared to 4°C PLTs. Systemic circulating levels of 4°C PLTs were decreased compared to 22°C PLTs.
  
  
  CONCLUSIONS
  In vitro, 4°C-stored PLTs exhibit a greater capacity to inhibit EC permeability than 22°C-stored PLTs. In vivo, 22°C PLTs provide superior control of vascular leak induced by VEGF-A. This discrepancy may be due to increased clearance of 4°C PLTs from the systemic circulation.
authors.affiliation: Blood Systems Research Institute, University of California, San Francisco, California.
authors.forename: Gyulnar
authors.initials: G
authors.lastname: Baimukanova
authors.affiliation: Department of Surgery, University of California, San Francisco, California.
authors.forename: Byron
authors.initials: B
authors.lastname: Miyazawa
authors.affiliation: Blood Systems Research Institute, University of California, San Francisco, California.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Potter
authors.affiliation: Blood Systems Research Institute, University of California, San Francisco, California.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Gibb
authors.affiliation: Blood Systems Research Institute, University of California, San Francisco, California.
authors.forename: Sheila
authors.initials: S
authors.lastname: Keating
authors.affiliation: Blood Systems Research Institute, University of California, San Francisco, California.|Department of Laboratory Medicine, University of California, San Francisco, California.
authors.forename: Ali
authors.initials: A
authors.lastname: Danesh
authors.affiliation: Blood Systems Research Institute, University of California, San Francisco, California.
authors.forename: Ashley
authors.initials: A
authors.lastname: Beyer
authors.affiliation: Blood Systems Research Institute, University of California, San Francisco, California.
authors.forename: Yelena
authors.initials: Y
authors.lastname: Dayter
authors.affiliation: Blood Systems Research Institute, University of California, San Francisco, California.
authors.forename: Roberta
authors.initials: R
authors.lastname: Bruhn
authors.affiliation: Blood Systems Research Institute, University of California, San Francisco, California.
authors.forename: Marcus O
authors.initials: MO
authors.lastname: Muench
authors.affiliation: Coagulation and Blood Research Program, US Army Institute of Surgical Research, JBSA-FT Sam Houston, Texas.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Cap
authors.affiliation: Blood Systems Research Institute, University of California, San Francisco, California.|Department of Laboratory Medicine, University of California, San Francisco, California.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Norris
authors.affiliation: Department of Pediatrics, Washington University in St Louis, St Louis, Missouri.
authors.forename: Philip
authors.initials: P
authors.lastname: Spinella
authors.affiliation: Department of Surgery, University of California, San Francisco, California.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Cohen
authors.affiliation: Blood Systems Research Institute, University of California, San Francisco, California.|Department of Laboratory Medicine, University of California, San Francisco, California.
authors.forename: Shibani
authors.initials: S
authors.lastname: Pati
mesh_terms: D000818:Animals; D001792:Blood Platelets; D001793:Blood Preservation; D002199:Capillary Permeability; D003080:Cold Temperature; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006358:Hot Temperature; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013997:Time Factors