title: Platelets regulate vascular endothelial stability: assessing the storage lesion and donor variability of apheresis platelets.
abstract: BACKGROUND
  In current blood banking practices, platelets (PLTs) are stored in plasma at 22°C, with gentle agitation for up to 5 days. To date, the effects of storage and donor variability on PLT regulation of vascular integrity are not known.
  
  
  METHODS
  In this study, we examined the donor variability of leukoreduced fresh (Day 1) or stored (Day 5) PLTs on vascular endothelial barrier function in vitro and in vivo. In vitro, PLT effects on endothelial cell (EC) monolayer permeability were assessed by analyzing transendothelial electrical resistances (TEER). PLT aggregation, a measure of hemostatic potential, was analyzed by impedance aggregometry. In vivo, PLTs were investigated in a vascular endothelial growth factor A (VEGF-A)-induced vascular permeability model in NSG mice, and PLT circulation was measured by flow cytometry.
  
  
  RESULTS
  Treatment of endothelial monolayers with fresh Day 1 PLTs resulted in an increase in EC barrier resistance and decreased permeability in a dose-dependent manner. Subsequent treatment of EC monolayers with Day 5 PLTs demonstrated diminished vasculoprotective effects. Donor variability was noted in all measures of PLT function. Day 1 PLT donors were more variable in their effects on TEER than Day 5 PLTs. In mice, while all PLTs regardless of storage time demonstrated significant protection against VEGF-A-induced vascular leakage, Day 5 PLTs exhibited reduced protection when compared to Day 1 PLTs. Day 1 PLTs demonstrated significant donor variability against VEGF-A-challenged vascular leakage in vivo. Systemic circulating levels of Day 1 PLTs were higher than those of Day 5 PLTs
  
  
  CONCLUSIONS
  In vitro and in vivo, Day 1 PLTs are protective in measures of vascular endothelial permeability. Donor variability is most prominent in Day 1 PLTs. A decrease in the protective effects is found with storage of the PLT units between Day 1 and Day 5 at 22°C, thereby suggesting that Day 5 PLTs are diminished in their ability to attenuate vascular endothelial permeability.
authors.affiliation: Blood Systems Research Institute, San Francisco, California.
authors.forename: Gyulnar
authors.initials: G
authors.lastname: Baimukanova
authors.affiliation: Department of Surgery, University of California at San Francisco, San Francisco, California.
authors.forename: Byron
authors.initials: B
authors.lastname: Miyazawa
authors.affiliation: Blood Systems Research Institute, San Francisco, California.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Potter
authors.affiliation: Blood Systems Research Institute, San Francisco, California.
authors.forename: Marcus O
authors.initials: MO
authors.lastname: Muench
authors.affiliation: Blood Systems Research Institute, San Francisco, California.
authors.forename: Roberta
authors.initials: R
authors.lastname: Bruhn
authors.affiliation: Blood Systems Research Institute, San Francisco, California.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Gibb
authors.affiliation: Division of Critical Care Medicine, Department of Pediatrics, Washington University School of Medicine in St Louis, St Louis, Missouri.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Spinella
authors.affiliation: US Army Institute of Surgical Research (USAISR), JBSA-FT Sam Houston, Texas.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Cap
authors.affiliation: Department of Surgery, University of California at San Francisco, San Francisco, California.
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Cohen
authors.affiliation: Blood Systems Research Institute, San Francisco, California.|Department of Laboratory Medicine, University of California at San Francisco, San Francisco, California.
authors.forename: Shibani
authors.initials: S
authors.lastname: Pati
mesh_terms: D000818:Animals; D001782:Blood Donors; D001792:Blood Platelets / Q000378:metabolism*; D001793:Blood Preservation; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D010983:Plateletpheresis; D013997:Time Factors