title: Increasing susceptibility of nitric oxide-mediated inhibitory platelet signaling during storage of apheresis-derived platelet concentrates.
abstract: BACKGROUND
  Storage of platelets (PLTs) affects PLT integrity and functionality, a process named the PLT storage lesion. Normal PLT function essentially depends on the balanced interaction of activating and inhibitory signaling pathways. As there are poor data on the alterations of inhibitory signaling during storage of PLT concentrates, this study investigates the modulation capability of the cyclic nucleotide-mediated inhibitory pathways by use of the nitric oxide donor diethylamine diazenium diolate (DEA/NO).
  
  
  METHODS
  PLTs were obtained from whole blood (WB) and from apheresis-derived PLT concentrates (APCs) stored for 0, 2, and 5 days. Vasodilator-stimulated phosphoprotein (VASP) phosphorylation, cyclic nucleotide concentrations, fibrinogen binding, and agonist-induced aggregation were measured without or after stimulation with DEA/NO.
  
  
  RESULTS
  DEA/NO-induced VASP phosphorylation was significantly higher in PLTs from APCs on Days 2 and 5 compared to WB, conditioned by a stronger increase of cyclic guanosine monophosphate (cGMP), but not cyclic adenosine monophosphate (cAMP), in stored PLTs. A quantity of 5 nmol/L DEA/NO neither influenced thrombin receptor activator peptide 6 and collagen-induced aggregation nor fibrinogen binding in freshly collected PLTs, whereas it significantly inhibited both in stored PLTs.
  
  
  CONCLUSIONS
  Stored PLTs showed an impairment of intracellular cGMP regulation, resulting in exceeding inhibition of agonist-induced aggregation and fibrinogen binding in the course of storage. The observed effects could be an important mechanism contributing to the storage lesion with reduced activating potential of PLTs.
authors.affiliation: Institute of Transfusion Medicine and Haemotherapy, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Kobsar
authors.forename: Erdwine
authors.initials: E
authors.lastname: Klinker
authors.forename: Sabine
authors.initials: S
authors.lastname: Kuhn
authors.forename: Angela
authors.initials: A
authors.lastname: Koessler
authors.forename: Pinar
authors.initials: P
authors.lastname: Yilmaz
authors.forename: Markus
authors.initials: M
authors.lastname: Boeck
authors.forename: Juergen
authors.initials: J
authors.lastname: Koessler
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D001793:Blood Preservation / Q000009:adverse effects*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010983:Plateletpheresis; D013997:Time Factors; D055815:Young Adult
chemical_list: D009569:Nitric Oxide; D005340:Fibrinogen