Use of mouse models to study the mechanisms and consequences of RBC clearance

Hod, Eldad A.; Arinsburg, Suzanne; Francis, Richard O.; Hendrickson, Jeanne E.; Zimring, James C.; Spitalnik, Steven L.

doi:10.1111/j.1423-0410.2010.01327.x

Cited by 28 publications

(35 citation statements)

References 130 publications

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“…UbiC‐GFP into B6), which model the autologous setting. This is not to say that there are not likely to be alloantigenic differences between RBCs from different strains; indeed, mouse strains are known to have erythrocyte alloantigens . However, because adaptive immunity takes days to weeks to form a primary antibody response, alloantibodies would not be expected to be present during the first 24‐h after transfusion.…”

Section: Discussionmentioning

confidence: 99%

Analysis of 24‐h recovery of transfused stored RBCs in recipient mice of distinct genetic backgrounds

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Analysis of 24‐h recovery of transfused stored RBCs in recipient mice of distinct genetic backgrounds

et al. 2015

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“…Unlike models of transplantation, RBCs isolated from different strains of mice do not inherently express distinct alloantigens capable of inducing RBC alloantibodies observed clinically following transfusion (14, 15). As a result, although RBC transfusion–induced alloantibody formation predates transplantation and has been recognized for nearly 80 y, models to study this process have historically not been available.…”

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confidence: 99%

Antigen Density Dictates Immune Responsiveness following Red Blood Cell Transfusion

Arthur

Patel

Smith

et al. 2017

The Journal of Immunology

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Although RBC transfusion can result in the development of anti-RBC alloantibodies that increase the probability of life-threatening hemolytic transfusion reactions, not all patients generate anti-RBC alloantibodies. However, the factors that regulate immune responsiveness to RBC transfusion remain incompletely understood. One variable that may influence alloantibody formation is RBC alloantigen density. RBC alloantigens exist at different densities on the RBC surface and likewise exhibit distinct propensities to induce RBC alloantibody formation. However, although distinct alloantigens reside on the RBC surface at different levels, most alloantigens also represent completely different structures, making it difficult to separate the potential impact of differences in Ag density from other alloantigen features that may also influence RBC alloimmunization. To address this, we generated RBCs that stably express the same Ag at different levels. Although exposure to RBCs with higher Ag levels induces a robust Ab response, RBCs bearing low Ag levels fail to induce RBC alloantibodies. However, exposure to low Ag–density RBCs is not without consequence, because recipients subsequently develop Ag-specific tolerance. Low Ag–density RBC–induced tolerance protects higher Ag–density RBCs from immune-mediated clearance, is Ag specific, and occurs through the induction of B cell unresponsiveness. These results demonstrate that Ag density can potently impact immune outcomes following RBC transfusion and suggest that RBCs with altered Ag levels may provide a unique tool to induce Ag-specific tolerance.

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“…Instead measuring cell survival was the best option. There are several approaches to this including chromium labeling [34], direct biotinylation [35], fluorescent dyes [13] or green fluorescent protein [36]. The approach we used was FSL biotinylation rather than the direct biotinylation method [35].…”

Section: Monitoring Transfusion Reactionsmentioning

confidence: 99%

“…The reader is referred elsewhere for papers on this topic [1][2][3][4][5][6][7][8]. Murine models are suitable for the study of the mechanisms and consequences of red cell clearance, despite some molecular and immunological response differences to humans [9][10][11][12][13]. For example, the CD receptors, which are essential for binding to lipid-based antigens (e.g.…”

Section: Introductionmentioning

confidence: 99%

Modeling transfusion reactions with kodecytes and enabling ABO‐incompatible transfusion with function‐spacer‐lipid constructs

Henry

Barr

Oliver

2012

ISBT Science Series

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Background KODE technology uses Function‐Spacer‐Lipid (FSL) constructs for artificial attachment of blood group antigens onto live cells (kodecytes) and visualisation, thus making it potentially suitable to model both transfusion reactions and determine in vivo cell survival. Additionally, as some FSL constructs are glycolipid‐like, the possibility exists that they may also neutralise circulating antibodies, in the same way Lewis glycolipids were historically used to allow Lewis incompatible transfusions. Aims To determine if kodecytes can be used to both mimic and monitor transfusion reactions in an animal model, and also to determine if FSL construct infusions can neutralise circulating antibodies and allow for an incompatible transfusion. Methods Naïve, anti‐A positive (immunised), and anti‐A positive/FSL‐A neutralised mice were given transfusions of murine kodecytes created with FSL‐biotin and FSL‐A. Levels of surviving kodecytes were determined at multiple time‐points via their biotin label. Analysis for anti‐A was performed with inkjet printed FSL‐A constructs in a micro immunoassay. Results Normal kodecyte survival was observed in control animals. Mice with anti‐A predominantly cleared their incompatible A‐kodecyte transfusions within 6 min. Mice with anti‐A that had been neutralised with an FSL‐A infusion had normal survival of their incompatible A‐kodecyte transfusions. Re‐challenge transfusions of A‐kodecytes into mice previously given FSL‐A (once the FSL‐A had cleared from their circulation) gave two different results. One group cleared the incompatible A‐kodecytes within minutes while the other had normal survival, suggesting potential induction of tolerance. Conclusions Kodecytes can be used to model blood group A incompatible transfusions in animals. FSL‐A can neutralise anti‐A and allow for incompatible A‐kodecyte transfusion. The potential exists to extend these research observations into clinical use to allow for transfusion and transplantation across the ABO barrier, or at least mitigate the consequences of accidental ABO incompatibilities.

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Use of mouse models to study the mechanisms and consequences of RBC clearance

Cited by 28 publications

References 130 publications

Analysis of 24‐h recovery of transfused stored RBCs in recipient mice of distinct genetic backgrounds

Analysis of 24‐h recovery of transfused stored RBCs in recipient mice of distinct genetic backgrounds

Antigen Density Dictates Immune Responsiveness following Red Blood Cell Transfusion

Modeling transfusion reactions with kodecytes and enabling ABO‐incompatible transfusion with function‐spacer‐lipid constructs

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