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- Title
Transfusion-related acute lung injury: critical neutrophil activation by anti-HLA-A2 antibodies for endothelial permeability.
- Authors
Khoy, Kathy; Nguyen, Minh Vu Chuong; Masson, Dominique; Bardy, Béatrice; Drouet, Christian; Paclet, Marie-Hélène
- Abstract
<bold>Background: </bold>Transfusion-related acute lung injury (TRALI) is a major complication of hemotherapy that may occur after the transfusion of any blood type component. Several clinical reports have suggested the presence of anti-HLA antibodies in the blood product. This study sought to examine the role of anti-HLA-A2 antibodies in polymorphonuclear neutrophil (PMN) activation and thus in endothelial permeability.<bold>Study Design and Methods: </bold>PMN activation was assessed by both nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) activity and reactive oxygen species (ROS) production. A coculture assay of EA.hy926 endothelial cells with PMNs or differentiated-PLB-985 cells, a model of neutrophil-like cells, was performed to estimate the impact of ROS on endothelial permeability.<bold>Results: </bold>Anti-HLA-A2 antibodies significantly increased PMN activation, with subsequent endothelial dysfunction. Phagocyte NADPH oxidase (NOX2) activity was shown to be involved in this process and ROS themselves were demonstrated to induce VE-cadherin cleavage and endothelial permeability.<bold>Conclusion: </bold>Our data may support the existence of a critical anti-HLA-A2 antibody threshold for PMN activation, with NOX2 activity and subsequent endothelial permeability in the two-hit model of TRALI.
- Subjects
BLOOD transfusion reaction; LUNG injury treatment; INTERLEUKIN-8 genetics; NEUTROPHILS; ENDOTHELIAL growth factors; PHYSIOLOGY; REACTIVE oxygen species; ANTIGENS; CELL lines; EPITHELIAL cells; GLYCOPROTEINS; IMMUNITY; IMMUNOGLOBULINS; LUNG injuries; OXIDOREDUCTASES; PERMEABILITY; HLA-B27 antigen; ACUTE diseases
- Publication
Transfusion, 2017, Vol 57, Issue 7, p1699
- ISSN
0041-1132
- Publication type
journal article
- DOI
10.1111/trf.14134