Abstract

Background - The use of omics technologies in human transfusion medicine has improved our understanding of the red blood cell (RBC) storage lesion(s). Despite significant progress towards understanding the storage lesion(s) of human RBCs, a comparison of basal and post-storage RBC metabolism across multiple species using omics technologies has not yet been reported, and is
the focus of this study.
Materials and methods - Blood was collected in a standard bag system (CPD-SAG-Mannitol) from dogs (n=8), horses, bovines, and donkeys (n=6). All bags were stored at 4°C for up to 42 days (i.e., the end of the shelf life in Italian veterinary clinics) and sampled weekly for metabolomics analyses. In addition, data comparisons to on our ongoing Zoomics project are included to compare this study’s results with those of non-human primates and humans.
Results - Significant interspecies differences in RBC metabolism were observed at baseline, at the time of donation, with bovine showing significantly higher levels of metabolites in the tryptophan/kynurenine pathway; dogs showing elevated levels of high-energy compounds (especially adenosine triphosphate and S-adenosyl-methionine) and equine (donkey and horse) RBCs showing almost overlapping phenotypes, with the highest levels of free branched chain amino acids, glycolytic metabolites (including 2,3-diphosphoglycerate), higher total glutathione pools, and elevated metabolites of the folate pathway compared to the other species. Strikingly, previously described metabolic markers of the storage lesion(s) in humans followed similar trends across all species, though the rate of accumulation/depletion of metabolites in energy and redox metabolism varied by species, with equine blood showing the
lowest degree of storage lesion(s).
Discussion - These results interrogate RBC metabolism across a range of mammalian species and improve our understanding of both human and veterinary blood storage and transfusion.

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Authors

Arianna Miglio - Department of Veterinary Medicine, University of Perugia, Perugia, Italy

Mark Maslanka - Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, United States of America

Morena Di Tommaso - Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy

Francesca Rocconi - Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy

Travis Nemkov - Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, United States of America

Paul W. Buehler - Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, United States of America; Department of Pediatrics, Center for Blood Oxygen Transport and Hemostasis, University of Maryland School of Medicine, Baltimore, MD, United States of America

Maria T. Antognoni - Department of Veterinary Medicine, University of Perugia, Perugia, Italy

Steven L. Spitalnik - Department of Pathology & Cell Biology, Columbia University, New York, NY, United States of America

Angelo D’Alessandro - Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, United States of America; Department of Medicine, Division of Hematology, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, United States of America

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