Tobias A Fuchs1, Javier J Alvarez, Kimberly Martinod, Ashish A Bhandari, Richard M Kaufman, Denisa D Wagner. 1. Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children's Hospital; Department of Pediatrics, Immunology Graduate Program, Division of Medical Sciences, Harvard Medical School; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
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.
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.
Authors: Paul C Hébert; Dean Fergusson; Morris A Blajchman; George A Wells; Andrew Kmetic; Doug Coyle; Nancy Heddle; Marc Germain; Mindy Goldman; Baldwin Toye; Irwin Schweitzer; Carl vanWalraven; Dana Devine; Graham D Sher Journal: JAMA Date: 2003-04-16 Impact factor: 56.272
Authors: Grace M Thomas; Carla Carbo; Brian R Curtis; Kimberly Martinod; Irina B Mazo; Daphne Schatzberg; Stephen M Cifuni; Tobias A Fuchs; Ulrich H von Andrian; John H Hartwig; Richard H Aster; Denisa D Wagner Journal: Blood Date: 2012-05-17 Impact factor: 22.113
Authors: Tobias A Fuchs; Johanna A Kremer Hovinga; Daphne Schatzberg; Denisa D Wagner; Bernhard Lämmle Journal: Blood Date: 2012-05-18 Impact factor: 22.113
Authors: Axelle Caudrillier; Kai Kessenbrock; Brian M Gilliss; John X Nguyen; Marisa B Marques; Marc Monestier; Pearl Toy; Zena Werb; Mark R Looney Journal: J Clin Invest Date: 2012-06-11 Impact factor: 14.808
Authors: Christopher C Silliman; Ernest E Moore; Jeffrey L Johnson; Ricardo J Gonzalez; Walter L Biffl Journal: Shock Date: 2004-04 Impact factor: 3.454
Authors: Maurits L van Montfoort; Femke Stephan; Mandy N Lauw; Barbara A Hutten; Gerard J Van Mierlo; Shabnam Solati; Saskia Middeldorp; Joost C M Meijers; Sacha Zeerleder Journal: Arterioscler Thromb Vasc Biol Date: 2012-10-25 Impact factor: 8.311
Authors: Mona Saffarzadeh; Christiane Juenemann; Markus A Queisser; Guenter Lochnit; Guillermo Barreto; Sebastian P Galuska; Juergen Lohmeyer; Klaus T Preissner Journal: PLoS One Date: 2012-02-28 Impact factor: 3.240
Authors: Ramanjaneyulu Allam; Santhosh V R Kumar; Murthy N Darisipudi; Hans-Joachim Anders Journal: J Mol Med (Berl) Date: 2014-04-06 Impact factor: 4.599
Authors: Miyuki Sakuma; Xiao Wang; Felix Ellett; Jon F Edd; Kehinde Adebayo Babatunde; Adam Viens; Michael K Mansour; Daniel Irimia Journal: Lab Chip Date: 2022-03-01 Impact factor: 6.799
Authors: Basile Tessier-Cloutier; David Dw Twa; Mahsa Marzban; Jennifer Kalina; Hye-Jung E Chun; Nils Pavey; Zaidi Tanweer; Ruth L Katz; Julian J Lum; Davide Salina Journal: J Pathol Clin Res Date: 2021-03-04
Authors: Chanchal Sur Chowdhury; Stavros Giaglis; Ulrich A Walker; Andreas Buser; Sinuhe Hahn; Paul Hasler Journal: Arthritis Res Ther Date: 2014-06-13 Impact factor: 5.156
Authors: Andrew W Shih; Vinai C Bhagirath; Nancy M Heddle; Jason P Acker; Yang Liu; John W Eikelboom; Patricia C Liaw Journal: J Blood Transfus Date: 2016-09-27
Authors: Keith H K Wong; Rebecca D Sandlin; Thomas R Carey; Kathleen L Miller; Aaron T Shank; Rahmi Oklu; Shyamala Maheswaran; Daniel A Haber; Daniel Irimia; Shannon L Stott; Mehmet Toner Journal: Sci Rep Date: 2016-02-15 Impact factor: 4.379