Abstract
Anemia and resultant red blood cell transfusion may be associated with adverse long-term clinical outcomes. To investigate the mechanism(s) responsible, we profiled inflammatory biomarkers and circulating levels of the bioactive lysophospholipid mediator sphingosine-1-phosphate (S1P) in control and anemic mice with or without LPS-induced systemic inflammation. Acute anemia or lipopolysaccharide (LPS) challenge alone triggered an increase of circulating levels of the inflammatory markers IL-6 and keratinocyte-derived chemokine (CXCL1/KC). Moreover, administration of LPS to anemic mice reduced circulating S1P levels and augmented lung injury and pulmonary vascular permeability. Transfusion of aged, but not fresh, red blood cells (RBCs) worsened pulmonary vascular leak. S1P levels decline markedly during storage of mouse RBCs. Loading stored murine RBCs with S1P prior to transfusion partially attenuated anemia-associated acute pulmonary vascular leak. Taken together, our results indicate that anemia and systemic inflammation can alter the S1P buffering capacity of RBCs, suggesting possible strategies for alleviating transfusion-related lung injury in clinical practice.
Highlights
Blood or packed erythrocytes are commonly administered to individuals with anemia, especially in settings of trauma and critical illness
Acute anemia or lipopolysaccharide (LPS) challenge alone triggered an increase of circulating levels of the inflammatory markers IL-6 and keratinocyte-derived chemokine (CXCL1/KC)
A recent study indicates that transfusion of fresh red blood cells (RBCs) counteracts the adverse effects of aged RBC on systemic inflammation [6], implying that older RBCs have lost a protective factor during storage, the identification of the factor remains unknown
Summary
Blood or packed erythrocytes are commonly administered to individuals with anemia, especially in settings of trauma and critical illness. In patients with acute respiratory distress and multiorgan failure, red blood cell (RBC) transfusion can promote acute lung injury and may predict mortality. The age of the transfused blood may be important, as alterations during storage may occur. The factor(s) responsible for tissue injury in the setting of transfusion remain to be identified. Any one—or a combination of these phenomena—could produce systemic inflammation, disrupt the integrity of the endothelial barrier, and promote tissue edema and leukocyte infiltration in susceptible recipients [5]. A recent study indicates that transfusion of fresh RBC counteracts the adverse effects of aged RBC on systemic inflammation [6], implying that older RBCs have lost a protective factor during storage, the identification of the factor remains unknown
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