Loss of red cell chemokine scavenging promotes transfusion-related lung inflammation.
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 endotoxemic 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.
Mangalmurti
Nilam S
NS
Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, PA 15213, USA.
Xiong
Zeyu
Z
Hulver
Mei
M
Ranganathan
Mrunalini
M
Liu
Xiang Hong
XH
Oriss
Timothy
T
Fitzpatrick
Meghan
M
Rubin
Marc
M
Triulzi
Darrell
D
Choi
Augustine
A
Lee
Janet S
JS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D055371:Acute Lung Injury / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects / Q000235:genetics; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000235:genetics / Q000378:metabolism; D016638:Critical Illness; D004375:Duffy Blood-Group System / Q000235:genetics / Q000378:metabolism; D019446:Endotoxemia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000378:metabolism / Q000473:pathology; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000235:genetics; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D011014:Pneumonia / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011309:Preservation, Biological; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
C473745:ACKR1 protein, human; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D004375:Duffy Blood-Group System; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; C483025:Ackr1 protein mouse