title: Loss of red cell chemokine scavenging promotes transfusion-related lung inflammation.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, PA 15213, USA.
authors.forename: Nilam S
authors.initials: NS
authors.lastname: Mangalmurti
authors.forename: Zeyu
authors.initials: Z
authors.lastname: Xiong
authors.forename: Mei
authors.initials: M
authors.lastname: Hulver
authors.forename: Mrunalini
authors.initials: M
authors.lastname: Ranganathan
authors.forename: Xiang Hong
authors.initials: XH
authors.lastname: Liu
authors.forename: Timothy
authors.initials: T
authors.lastname: Oriss
authors.forename: Meghan
authors.initials: M
authors.lastname: Fitzpatrick
authors.forename: Marc
authors.initials: M
authors.lastname: Rubin
authors.forename: Darrell
authors.initials: D
authors.lastname: Triulzi
authors.forename: Augustine
authors.initials: A
authors.lastname: Choi
authors.forename: Janet S
authors.initials: JS
authors.lastname: Lee
mesh_terms: 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
chemical_list: 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