Neutrophils release extracellular DNA traps during storage of red blood cell units

Authors

  • Tobias A. Fuchs,

    1. Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children's Hospital
    2. Department of Pediatrics, Immunology Graduate Program, Division of Medical Sciences, Harvard Medical School
    3. Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts
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  • Javier J. Alvarez,

    1. Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children's Hospital
    2. Department of Pediatrics, Immunology Graduate Program, Division of Medical Sciences, Harvard Medical School
    3. Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts
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  • Kimberly Martinod,

    1. Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children's Hospital
    2. Department of Pediatrics, Immunology Graduate Program, Division of Medical Sciences, Harvard Medical School
    3. Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts
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  • Ashish A. Bhandari,

    1. Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children's Hospital
    2. Department of Pediatrics, Immunology Graduate Program, Division of Medical Sciences, Harvard Medical School
    3. Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts
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  • Richard M. Kaufman,

    1. Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children's Hospital
    2. Department of Pediatrics, Immunology Graduate Program, Division of Medical Sciences, Harvard Medical School
    3. Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts
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  • Denisa D. Wagner

    Corresponding author
    1. Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children's Hospital
    2. Department of Pediatrics, Immunology Graduate Program, Division of Medical Sciences, Harvard Medical School
    3. Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts
    • Address reprint requests to: Denisa D. Wagner, PhD, Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, 3 Blackfan Circle, Third Floor, Boston, MA 02115; e-mail: Denisa.Wagner@childrens.harvard.edu.

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  • This work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health Grant R01 HL102101 (DDW).

Abstract

Background

Blood transfusion is associated with an increased risk of organ damage, infection, and alloimmunity. Neutrophil extracellular traps (NETs) are extracellular chromatin fibers decorated with neutrophil granular proteins that have been linked to cytotoxicity, thrombosis, and autoimmunity. We questioned whether neutrophils in blood products release NETs during storage and thus could contribute to adverse reactions from blood transfusions.

Study Design and Methods

We analyzed supernatants and blood smears of human red blood cell (RBC) units that either were or were not leukoreduced before storage for markers of NETs.

Results

We identified extracellular DNA, which was associated with histones and myeloperoxidase, a marker of neutrophil granules, in supernatants and blood smears of nonleukoreduced RBC units. These markers of NETs were absent in leukoreduced RBC units. Importantly, NETs passed through blood transfusion filters and could therefore potentially be infused into patients.

Conclusions

Our studies indicate that NETs are liberated during storage of nonleukoreduced RBC units. Future studies should address whether NETs in RBC units could potentially contribute to transfusion-associated complications.

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