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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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Submitted July 1, 2008
Accepted November 25, 2008
Loss of red cell chemokine scavenging promotes transfusion related lung inflammation
Nilam S Mangalmurti, Zeyu Xiong, Mei Hulver, Mrunalini Ranganathan, Xiang Hong Liu, Timothy Oriss, Meghan Fitzpatrick, Marc Rubin, Darrell Triulzi, Augustine Choi, and Janet S. Lee*
Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, United States
Center for Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
Division of Transfusion Medicine, Department of Pathology, University of Pittsburgh, Pittsburgh, PA, United States
Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
* Corresponding author; email: leejs3{at}upmc.edu.
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 cell collectively termed the "storage lesion" may be linked with adverse biological consequences. Using a two event model of systemic endotoxemia followed by a secondary challenge of red cell transfusion, we investigated whether purified red cell concentrates from syngeneic C57Bl/6 mice altered inflammatory responses in murine lungs. Transfusion of packed red cells (RBC) stored for 10 days increased neutrophil counts, MIP-2 and KC concentrations in the airspaces, and lung microvascular permeability when compared with transfusion of < 1 d old RBC. Because red cells have been shown to scavenge inflammatory chemokines through the blood group Duffy antigen (Fy), we investigated the expression and function of Fy during storage. In banked human RBC, both Fy expression and chemokine scavenging function were reduced with increasing duration of storage. Furthermore, transfusion of Fy-/- RBC into Fy+/+ endotoxemic mice increased airspace neutrophils, inflammatory cytokine concentrations, and lung microvascular permeability compared to transfusion of Fy+/+ RBC. 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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