title: Acid Sphingomyelinase Inhibition in Stored Erythrocytes Reduces Transfusion-Associated Lung Inflammation.
abstract: We aimed to identify the role of the enzyme acid sphingomyelinase in the aging of stored units of packed red blood cells (pRBCs) and subsequent lung inflammation after transfusion.
  
  
  
  Large volume pRBC transfusions are associated with multiple adverse clinical sequelae, including lung inflammation. Microparticles are formed in stored pRBCs over time and have been shown to contribute to lung inflammation after transfusion.
  
  
  
  Human and murine pRBCs were stored with or without amitriptyline, a functional inhibitor of acid sphingomyelinase, or obtained from acid sphingomyelinase-deficient mice, and lung inflammation was studied in mice receiving transfusions of pRBCs and microparticles isolated from these units.
  
  
  
  Acid sphingomyelinase activity in pRBCs was associated with the formation of ceramide and the release of microparticles. Treatment of pRBCs with amitriptyline inhibited acid sphingomyelinase activity, ceramide accumulation, and microparticle production during pRBC storage. Transfusion of aged pRBCs or microparticles isolated from aged blood into mice caused lung inflammation. This was attenuated after transfusion of pRBCs treated with amitriptyline or from acid sphingomyelinase-deficient mice.
  
  
  
  Acid sphingomyelinase inhibition in stored pRBCs offers a novel mechanism for improving the quality of stored blood.
authors.affiliation: *Department of Surgery and Institute for Military Medicine, University of Cincinnati, Cincinnati, OH †Department of Toxicology, Institute of Nutritional Science, University of Potsdam, Germany ‡Department of Molecular Biology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Hoehn
authors.forename: Peter L
authors.initials: PL
authors.lastname: Jernigan
authors.forename: Lukasz
authors.initials: L
authors.lastname: Japtok
authors.forename: Alex L
authors.initials: AL
authors.lastname: Chang
authors.forename: Emily F
authors.initials: EF
authors.lastname: Midura
authors.forename: Charles C
authors.initials: CC
authors.lastname: Caldwell
authors.forename: Burkhard
authors.initials: B
authors.lastname: Kleuser
authors.forename: Alex B
authors.initials: AB
authors.lastname: Lentsch
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Edwards
authors.forename: Erich
authors.initials: E
authors.lastname: Gulbins
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Pritts
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001793:Blood Preservation / Q000009:adverse effects / Q000379:methods*; D055252:Cell-Derived Microparticles / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D017707:Erythrocyte Transfusion / Q000009:adverse effects*; D004912:Erythrocytes / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors* / Q000172:deficiency
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; D000639:Amitriptyline; D013108:Sphingomyelin Phosphodiesterase