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Blood, 29 January 2009, Vol. 113, No. 5, pp. 1158-1166.
Prepublished online as a Blood First Edition Paper on December 8, 2008; DOI 10.1182/blood-2008-07-166264.


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TRANSFUSION MEDICINE

Loss of red cell chemokine scavenging promotes transfusion-related lung inflammation

Nilam S. Mangalmurti1, Zeyu Xiong1, Mei Hulver1, Mrunalini Ranganathan1, Xiang Hong Liu1, Timothy Oriss1, Meghan Fitzpatrick1, Marc Rubin2, Darrell Triulzi3, Augustine Choi4, and Janet S. Lee1

1 Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, 2 Center for Biologic Imaging, and 3 Division of Transfusion Medicine, Department of Pathology, University of Pittsburgh, PA; and 4 Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA

Red cell transfusions are associated with the development of acute lung injury in the critically ill. Recent evidence suggests that storage induced alterations of the red blood cell (RBC) collectively termed the "storage lesion" may be linked with adverse biologic consequences. Using a 2-event model of systemic endotoxemia followed by a secondary challenge of RBC transfusion, we investigated whether purified RBC concentrates from syngeneic C57BL/6 mice altered inflammatory responses in murine lungs. Transfusion of RBCs stored for 10 days increased neutrophil counts, macrophage inflammatory protein-2 (MIP-2) and chemokine (KC) concentrations in the airspaces, and lung microvascular permeability compared with transfusion of less than 1-day-old RBCs. Because RBCs have been shown to scavenge inflammatory chemokines through the blood group Duffy antigen, we investigated the expression and function of Duffy during storage. In banked human RBCs, both Duffy expression and chemokine scavenging function were reduced with increasing duration of storage. Transfusion of Duffy knockout RBCs into Duffy wild-type en-dotoxemic mice increased airspace neutrophils, inflammatory cytokine concentrations, and lung microvascular permeability compared with transfusion of Duffy wild-type RBCs. Thus, reduction in erythrocyte chemokine scavenging is one functional consequence of the storage lesion by which RBC transfusion can augment existing lung inflammation.


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