Mechanisms Underlying Impaired Bacterial Clearance Following Transfusion of Storage-Damaged Red Blood Cells

Red blood cell (RBC) transfusions are a common therapy utilized in hospitals, with ~15 million RBC units administered annually in the United States. RBC transfusions are associated with multiple adverse effects, including an increased risk for bacterial infection. Before transfusion, donor RBCs are refrigerator-stored for up to 42 days, as established by FDA criteria. During storage, RBCs undergo multiple structural and metabolic alterations, collectively known as ?the storage lesion.? As a result, some storage-damaged RBCs are rapidly cleared from the circulation post-transfusion, a process mediated predominantly by phagocytic cells in the spleen and liver (i.e., ?extravascular hemolysis?). Although several studies were designed to observe the incidence of adverse effects following transfusions of stored RBCs, very little is known about the underlying mechanisms causing these adverse effects. Therefore, to identify potential mechanisms, we will use a novel mouse model of RBC storage and clearance. Our Laboratory has successfully used this model previously and observed that mice are more susceptible to bacterial infection following transfusions of storage-damaged RBCs, which are cleared by extravascular hemolysis. Therefore, we believe that mouse models offer tremendous potential for achieving the overall aim of this project, which is to investigate the mechanism(s) by which hemolysis leads to an increased risk of bacterial infections, with our overall hypothesis being that robust erythrophagocytosis by macrophages impairs bacterial phagocytosis during a subsequent infection.