A novel mouse model of red blood cell storage and posttransfusion in vivo survival

Gilson, Christopher R.; Kraus, Teresa; Hod, Eldad A.; Hendrickson, Jeanne E.; Spitalnik, Steven L.; Hillyer, Christopher D.; Shaz, Beth H.; Zimring, James C.

doi:10.1111/j.1537-2995.2009.02173.x

Cited by 106 publications

(158 citation statements)

References 16 publications

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“…24,25,36 Hod et al 37 recently found free iron released from damaged stored RBC to amplify LPS-induced inflammation in a murine transfusion model. Despite differences in RBC purification and storage conditions between our study and the work by Hod and co-workers, 35,37 several findings are consistent. First, the amount of stored RBC we used to prepare RBC-MV was comparable with that used by Hod et al for injection of stored RBC supernatants or hemolysates.…”

Section: Discussionsupporting

confidence: 78%

“…This included dextran sedimentation for RBC enrichment and MV purification from RBC aged longer than what is thought to be equivalent to the human maximum storage time of 42 days. 35 These differences might were given 1×10 9 RBC-MV intravenously 15 minutes later, plasma was obtained, and C5a levels (B) and thrombin activity (C) were determined by ELISA and a thrombin assay, respectively, as indicated in Methods in the online-only Data Supplement. Amplification of pulmonary polymorphonuclear cells (PMN) sequestration (D) and systemic inflammation (E) in LPS-primed B6 mice 4 hours after injection of RBC-MV can be reversed by refludan.…”

Section: Discussionmentioning

confidence: 99%

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Erythrocyte-Derived Microvesicles Amplify Systemic Inflammation by Thrombin-Dependent Activation of Complement

Zecher

Čumpelik

Schifferli

2014

ATVB

111

100

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Objective-Transfusion of aged blood has been associated with increased morbidity and mortality in critically ill patients.During storage, erythrocytes release increasing numbers of microvesicles (red blood cell-derived microvesicles [RBC-MV]). We hypothesized that RBC-MV mediate some of the deleterious effects of aged blood transfusions. Approach and Results-We established a murine transfusion model using RBC-MV purified from aged mouse erythrocytes. Injection of RBC-MV into healthy mice had no effect. However, they aggravated pulmonary leukocyte sequestration and peripheral blood leukopenia induced by lipopolysaccharides. Lipopolysaccharide-induced proinflammatory cytokines were significantly increased in plasma after RBC-MV injection. These effects were not seen in C5aR-deficient mice. In vitro, RBC-MV bound C3 fragments after incubation with plasma but failed to bind immunoglobulins, C1q, or mannose-binding lectin. Preventing thrombin generation inhibited complement activation in vitro and in vivo and reversed the proinflammatory effects of RBC-MV in lipopolysaccharide-primed mice. Finally, the RBC-MV-induced phenotype was recapitulated using phosphatidylserineexpressing liposomes, suggesting that surface expression of phosphatidylserine by RBC-MV was mechanistically involved. Conclusions-These

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Erythrocyte-Derived Microvesicles Amplify Systemic Inflammation by Thrombin-Dependent Activation of Complement

Zecher

Čumpelik

Schifferli

2014

ATVB

111

100

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“…mice. 22,23 Gilson et al 24 as well as Hod et al 25 reported that after 14 days of storage in CPDA-1, murine RBCs had an in vivo 24-h RBC recovery of 64% to 65%, which is similar to the data from human RBCs stored for 42 days. 26 Yu et al reproduced the mature model, characterized the biochemical and functional effects, and studied the mechanisms responsible for the adverse effects of transfusing stored RBCs.…”

Section: Discussionsupporting

confidence: 76%

The mechanical properties of stored red blood cells measured by a convenient microfluidic approach combining with mathematic model

et al. 2016

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The mechanical properties of red blood cells (RBCs) are critical to the rheological and hemodynamic behavior of blood. Although measurements of the mechanical properties of RBCs have been studied for many years, the existing methods, such as ektacytometry, micropipette aspiration, and microfluidic approaches, still have limitations. Mechanical changes to RBCs during storage play an important role in transfusions, and so need to be evaluated pre-transfusion, which demands a convenient and rapid detection method. We present a microfluidic approach that focuses on the mechanical properties of single cell under physiological shear flow and does not require any high-end equipment, like a high-speed camera. Using this method, the images of stretched RBCs under physical shear can be obtained. The subsequent analysis, combined with mathematic models, gives the deformability distribution, the morphology distribution, the normalized curvature, and the Young's modulus (E) of the stored RBCs. The deformability index and the morphology distribution show that the deformability of RBCs decreases significantly with storage time. The normalized curvature, which is defined as the curvature of the cell tail during stretching in flow, suggests that the surface charge of the stored RBCs decreases significantly. According to the mathematic model, which derives from the relation between shear stress and the adherent cells' extension ratio, the Young's moduli of the stored RBCs are also calculated and show significant increase with storage. Therefore, the present method is capable of representing the mechanical properties and can distinguish the mechanical changes of the RBCs during storage. The advantages of this method are the small sample needed, high-throughput, and easy-use, which make it promising for the quality monitoring of RBCs. V C 2016 AIP Publishing LLC.

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“…49 Recently, a novel mouse model showed that red cell transfusion of aged blood resulted in oxidative stress and inflammatory cytokine secretion in response to macrophage-ingested iron from membraneencapsulated hemoglobin, but not from stroma-free lysate derived from stored red cells. 74 Long-term effects of the intravenous iron preparations will require careful study in relevant clinical settings. 75,76 …”

Section: Intravenous Iron Therapymentioning

confidence: 99%

Detection, evaluation, and management of iron-restricted erythropoiesis

Goodnough

Nemeth

Ganz

2010

Blood

378

349

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A novel mouse model of red blood cell storage and posttransfusion in vivo survival

Cited by 106 publications

References 16 publications

Erythrocyte-Derived Microvesicles Amplify Systemic Inflammation by Thrombin-Dependent Activation of Complement

Erythrocyte-Derived Microvesicles Amplify Systemic Inflammation by Thrombin-Dependent Activation of Complement

The mechanical properties of stored red blood cells measured by a convenient microfluidic approach combining with mathematic model

Detection, evaluation, and management of iron-restricted erythropoiesis

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