Storage of erythrocytes in blood banks is associated with biochemical and morphological changes to RBCs (red blood cells). It has been suggested that these changes have potential negative clinical effects characterized by inflammation and microcirculatory dysfunction which add to other transfusion-related toxicities. However, the mechanisms linking RBC storage and toxicity remain unclear. In the present study we tested the hypothesis that storage of leucodepleted RBCs results in cells that inhibit NO (nitric oxide) signalling more so than younger cells. Using competition kinetic analyses and protocols that minimized contributions from haemolysis or microparticles, our data indicate that the consumption rates of NO increased ~40-fold and NO-dependent vasodilation was inhibited 2–4-fold comparing 42-day-old with 0-day-old RBCs. These results are probably due to the formation of smaller RBCs with increased surface area: volume as a consequence of membrane loss during storage. The potential for older RBCs to affect NO formation via deoxygenated RBC-mediated nitrite reduction was also tested. RBC storage did not affect deoxygenated RBC-dependent stimulation of nitrite-induced vasodilation. However, stored RBCs did increase the rates of nitrite oxidation to nitrate in vitro. Significant loss of whole-blood nitrite was also observed in stable trauma patients after transfusion with 1 RBC unit, with the decrease in nitrite occurring after transfusion with RBCs stored for >25 days, but not with younger RBCs. Collectively, these data suggest that increased rates of reactions between intact RBCs and NO and nitrite may contribute to mechanisms that lead to storage-lesion-related transfusion risk.
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September 2012
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Research Article|
August 28 2012
Erythrocyte storage increases rates of NO and nitrite scavenging: implications for transfusion-related toxicity
Ryan Stapley;
Ryan Stapley
*Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294., U.S.A.
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Benjamin Y. Owusu;
Benjamin Y. Owusu
*Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294., U.S.A.
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Angela Brandon;
Angela Brandon
*Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294., U.S.A.
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Marianne Cusick;
Marianne Cusick
†Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, U.S.A.
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Cilina Rodriguez;
Cilina Rodriguez
†Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, U.S.A.
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Marisa B. Marques;
Marisa B. Marques
*Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294., U.S.A.
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Jeffrey D. Kerby;
Jeffrey D. Kerby
†Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, U.S.A.
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Scott R. Barnum;
Scott R. Barnum
‡Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, U.S.A.
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Jordan A. Weinberg;
Jordan A. Weinberg
§Department of Anesthesiology University of Alabama at Birmingham, Birmingham, AL 35294, U.S.A.
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Jack R. Lancaster, Jr;
Jack R. Lancaster, Jr
¶Department of Surgery, University of Tennessee Health Science Center, Memphis, TN 38103, U.S.A.
∥Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL 35294, U.S.A.
**Department of Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, U.S.A.
††Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294, U.S.A.
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Rakesh P. Patel
*Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294., U.S.A.
††Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294, U.S.A.
2To whom correspondence should be addressed (email rakeshp@uab.edu).
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Publisher: Portland Press Ltd
Received:
April 24 2012
Revision Received:
June 15 2012
Accepted:
June 21 2012
Accepted Manuscript online:
June 21 2012
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem J (2012) 446 (3): 499–508.
Article history
Received:
April 24 2012
Revision Received:
June 15 2012
Accepted:
June 21 2012
Accepted Manuscript online:
June 21 2012
Citation
Ryan Stapley, Benjamin Y. Owusu, Angela Brandon, Marianne Cusick, Cilina Rodriguez, Marisa B. Marques, Jeffrey D. Kerby, Scott R. Barnum, Jordan A. Weinberg, Jack R. Lancaster, Rakesh P. Patel; Erythrocyte storage increases rates of NO and nitrite scavenging: implications for transfusion-related toxicity. Biochem J 15 September 2012; 446 (3): 499–508. doi: https://doi.org/10.1042/BJ20120675
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