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Synergistic effect of anemia and red blood cells transfusion on inflammation and lung injury.

Dong A, Sunkara M, Panchatcharam M, Salous A, Selim S, Morris AJ, Smyth SS - Adv Hematol (2012)

Bottom Line: Anemia and resultant red blood cell transfusion may be associated with adverse long-term clinical outcomes.Transfusion of aged, but not fresh, red blood cells (RBCs) worsened pulmonary vascular leak.Loading stored murine RBCs with S1P prior to transfusion partially attenuated anemia-associated acute pulmonary vascular leak.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiovascular Medicine, The Gill Heart Institute, 741 S. Limestone Street, 252 BBSRB, Lexington, KY 40536-0509, USA.

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.

No MeSH data available.


Related in: MedlinePlus

Effect of transfusion of fresh and aged RBC on systemic inflammation response and lung endothelial permeability. Twenty-four hours after major blood loss (0.02 mL/gm), mice were administered 0.3 mL of PBS (“vehicle”), freshly isolated RBC at 50% Hct (“fresh RBC”), or RBC stored for >14 days (“aged RBC”) at 50% Hct. Fortyeight hours after initial blood loss, (a) Hct, (b) plasma Il-6, (c) plasma KC, (d) white blood cell count (WBC), (e) blood S1P, and (f) lung endothelial permeability were measured. IL-6, KC, and S1P are reported as % of baseline (time 0). Results were analyzed by one-way ANOVA (Bonferroni correction),*P < 0.05 versus vehicle.
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fig2: Effect of transfusion of fresh and aged RBC on systemic inflammation response and lung endothelial permeability. Twenty-four hours after major blood loss (0.02 mL/gm), mice were administered 0.3 mL of PBS (“vehicle”), freshly isolated RBC at 50% Hct (“fresh RBC”), or RBC stored for >14 days (“aged RBC”) at 50% Hct. Fortyeight hours after initial blood loss, (a) Hct, (b) plasma Il-6, (c) plasma KC, (d) white blood cell count (WBC), (e) blood S1P, and (f) lung endothelial permeability were measured. IL-6, KC, and S1P are reported as % of baseline (time 0). Results were analyzed by one-way ANOVA (Bonferroni correction),*P < 0.05 versus vehicle.

Mentions: We next determined whether restoration of Hct by RBC transfusion 24 hours after blood loss had an impact on circulating inflammatory biomarkers or endothelial permeability. Administration of fresh (transfused on the day of isolation) or aged (stored for >14 days before transfusion) RBC improved Hct (Figure 2(a)). Transfusion of aged but not fresh RBC, increased plasma Il-6 and CXCL1/KC levels (Figures 2(b) and 2(c)), reduced white blood cell (WBC) count (Figure 2(d)), and modestly promoted lung endothelial permeability (Figure 2(f)). Following administration of fresh RBC, whole blood levels of S1P increased slightly, whereas they declined after administration of aged RBC (Figure 2(e)). To understand the reason for the differential effect of fresh and aged RBC on plasma S1P levels, we measured S1P content in RBC during storage and observed a steady decline over time (Supplementary Figure 4), such that the S1P content of erythrocytes stored for 30 days was <25% of that found in freshly isolated cells. Likewise, the dihdro-S1P (DHS1P) content of murine erythrocytes also decreased during storage (Supplementary Figure 4). These findings indicate that RBCs are 1 of at least 2 main sources for blood S1P in mice and that the S1P content of transfused RBCs affects blood S1P levels.


Synergistic effect of anemia and red blood cells transfusion on inflammation and lung injury.

Dong A, Sunkara M, Panchatcharam M, Salous A, Selim S, Morris AJ, Smyth SS - Adv Hematol (2012)

Effect of transfusion of fresh and aged RBC on systemic inflammation response and lung endothelial permeability. Twenty-four hours after major blood loss (0.02 mL/gm), mice were administered 0.3 mL of PBS (“vehicle”), freshly isolated RBC at 50% Hct (“fresh RBC”), or RBC stored for >14 days (“aged RBC”) at 50% Hct. Fortyeight hours after initial blood loss, (a) Hct, (b) plasma Il-6, (c) plasma KC, (d) white blood cell count (WBC), (e) blood S1P, and (f) lung endothelial permeability were measured. IL-6, KC, and S1P are reported as % of baseline (time 0). Results were analyzed by one-way ANOVA (Bonferroni correction),*P < 0.05 versus vehicle.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3420227&req=5

fig2: Effect of transfusion of fresh and aged RBC on systemic inflammation response and lung endothelial permeability. Twenty-four hours after major blood loss (0.02 mL/gm), mice were administered 0.3 mL of PBS (“vehicle”), freshly isolated RBC at 50% Hct (“fresh RBC”), or RBC stored for >14 days (“aged RBC”) at 50% Hct. Fortyeight hours after initial blood loss, (a) Hct, (b) plasma Il-6, (c) plasma KC, (d) white blood cell count (WBC), (e) blood S1P, and (f) lung endothelial permeability were measured. IL-6, KC, and S1P are reported as % of baseline (time 0). Results were analyzed by one-way ANOVA (Bonferroni correction),*P < 0.05 versus vehicle.
Mentions: We next determined whether restoration of Hct by RBC transfusion 24 hours after blood loss had an impact on circulating inflammatory biomarkers or endothelial permeability. Administration of fresh (transfused on the day of isolation) or aged (stored for >14 days before transfusion) RBC improved Hct (Figure 2(a)). Transfusion of aged but not fresh RBC, increased plasma Il-6 and CXCL1/KC levels (Figures 2(b) and 2(c)), reduced white blood cell (WBC) count (Figure 2(d)), and modestly promoted lung endothelial permeability (Figure 2(f)). Following administration of fresh RBC, whole blood levels of S1P increased slightly, whereas they declined after administration of aged RBC (Figure 2(e)). To understand the reason for the differential effect of fresh and aged RBC on plasma S1P levels, we measured S1P content in RBC during storage and observed a steady decline over time (Supplementary Figure 4), such that the S1P content of erythrocytes stored for 30 days was <25% of that found in freshly isolated cells. Likewise, the dihdro-S1P (DHS1P) content of murine erythrocytes also decreased during storage (Supplementary Figure 4). These findings indicate that RBCs are 1 of at least 2 main sources for blood S1P in mice and that the S1P content of transfused RBCs affects blood S1P levels.

Bottom Line: Anemia and resultant red blood cell transfusion may be associated with adverse long-term clinical outcomes.Transfusion of aged, but not fresh, red blood cells (RBCs) worsened pulmonary vascular leak.Loading stored murine RBCs with S1P prior to transfusion partially attenuated anemia-associated acute pulmonary vascular leak.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiovascular Medicine, The Gill Heart Institute, 741 S. Limestone Street, 252 BBSRB, Lexington, KY 40536-0509, USA.

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.

No MeSH data available.


Related in: MedlinePlus