Extracellular DNA traps are associated with the pathogenesis of TRALI in humans and mice. Blood 2012 Jun 28;119(26):6335-43
Date
05/19/2012Pubmed ID
22596262Pubmed Central ID
PMC3383196DOI
10.1182/blood-2012-01-405183Scopus ID
2-s2.0-84863502628 (requires institutional sign-in at Scopus site) 247 CitationsAbstract
Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related death. The biologic processes contributing to TRALI are poorly understood. All blood products can cause TRALI, and no specific treatment is available. A "2-event model" has been proposed as the trigger. The first event may include surgery, trauma, or infection; the second involves the transfusion of antileukocyte antibodies or bioactive lipids within the blood product. Together, these events induce neutrophil activation in the lungs, causing endothelial damage and capillary leakage. Neutrophils, in response to pathogens or under stress, can release their chromatin coated with granule contents, thus forming neutrophil extracellular traps (NETs). Although protective against infection, these NETs are injurious to tissue. Here we show that NET biomarkers are present in TRALI patients' blood and that NETs are produced in vitro by primed human neutrophils when challenged with anti-HNA-3a antibodies previously implicated in TRALI. NETs are found in alveoli of mice experiencing antibody-mediated TRALI. DNase 1 inhalation prevents their alveolar accumulation and improves arterial oxygen saturation even when administered 90 minutes after TRALI onset. We suggest that NETs form in the lungs during TRALI, contribute to the disease process, and thus could be targeted to prevent or treat TRALI.
Author List
Thomas GM, Carbo C, Curtis BR, Martinod K, Mazo IB, Schatzberg D, Cifuni SM, Fuchs TA, von Andrian UH, Hartwig JH, Aster RH, Wagner DDAuthor
Brian Curtis PhD Director in the Platelet & Neutrophil Immunology Laboratory department at BloodCenter of WisconsinMESH terms used to index this publication - Major topics in bold
Acute Lung InjuryAnimals
Blood Donors
Cells, Cultured
DNA
Extracellular Space
Humans
Male
Mice
Mice, Inbred BALB C
Neutrophil Activation
Neutrophils
Transfusion Reaction
Transplantation Immunology
Transplantation, Homologous
