title: Isoprostane and isofuran lipid mediators accumulate in stored red blood cells and influence platelet function in vitro.
abstract: BACKGROUND
  Stored red blood cells (RBCs) release hemoglobin (Hb) that leads to oxidative damage, which may contribute to thrombosis in susceptible transfusion recipients. Oxidative stress stimulates the generation of a new class of lipid mediators called F2 -isoprostanes (F2 -IsoPs) and isofurans (IsoFs) that influence cellular behavior. This study investigated RBC-derived F2 -IsoPs and IsoFs during storage and their influence on human platelets (PLTs).
  
  
  METHODS
  F2 -IsoP and IsoF levels in RBC supernatants were measured by mass spectrometry during storage and after washing. The effects of stored supernatants, cell-free Hb, or a key F2 -IsoP, 8-iso-prostaglandin F2α (PGF2α ), on PLT function were examined in vitro.
  
  
  RESULTS
  F2 -IsoPs, IsoFs, and Hb accumulated in stored RBC supernatants. Prestorage leukoreduction reduced supernatant F2 -IsoPs and IsoFs levels, which increased again over storage time. Stored RBC supernatants and 8-iso-PGF2α induced PLT activation marker CD62P (P-selectin) expression and prothrombotic thromboxane A2 release. Cell-free Hb did not alter PLT mediator release, but did inhibit PLT spreading. Poststorage RBC washing reduced F2 -IsoP and IsoF levels up to 24 hours.
  
  
  CONCLUSIONS
  F2 -IsoPs and IsoFs are produced by stored RBCs and induce adverse effects on PLT function in vitro, supporting a potential novel role for bioactive lipids in adverse transfusion outcomes. F2 -IsoP and IsoF levels could be useful biomarkers for determining the suitability of blood components for transfusion. A novel finding is that cell-free Hb inhibits PLT spreading and could adversely influence wound healing. Poststorage RBC washing minimizes harmful lipid mediators, and its use could potentially reduce transfusion complications.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York.
authors.forename: Sherry L
authors.initials: SL
authors.lastname: Spinelli
authors.forename: Katie L
authors.initials: KL
authors.lastname: Lannan
authors.forename: Ann E
authors.initials: AE
authors.lastname: Casey
authors.forename: Amanda
authors.initials: A
authors.lastname: Croasdell
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Curran
authors.forename: Kelly F
authors.initials: KF
authors.lastname: Henrichs
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Pollock
authors.forename: Ginger A
authors.initials: GA
authors.lastname: Milne
authors.forename: Majed A
authors.initials: MA
authors.lastname: Refaai
authors.forename: Charles W
authors.initials: CW
authors.lastname: Francis
authors.forename: Richard P
authors.initials: RP
authors.lastname: Phipps
authors.forename: Neil
authors.initials: N
authors.lastname: Blumberg
mesh_terms: D001792:Blood Platelets / Q000378:metabolism*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D028441:F2-Isoprostanes / Q000378:metabolism; D005663:Furans / Q000378:metabolism*; D006801:Humans; D007118:Immunoassay; D028421:Isoprostanes / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D028441:F2-Isoprostanes; D005663:Furans; D028421:Isoprostanes; D017382:Reactive Oxygen Species; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; C039281:furan