• Richard S Hoehn, Peter L Jernigan, Lukasz Japtok, Alex L Chang, Emily F Midura, Charles C Caldwell, Burkhard Kleuser, Alex B Lentsch, Michael J Edwards, Erich Gulbins, and Timothy A Pritts.
• *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.
• Ann. Surg. 2017 Jan 1; 265 (1): 218-226.

ObjectiveWe 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.Summary Background DataLarge 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.MethodsHuman 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.ResultsAcid 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.ConclusionsAcid sphingomyelinase inhibition in stored pRBCs offers a novel mechanism for improving the quality of stored blood.

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