Transfusion-related acute lung injury: critical neutrophil activation by anti-HLA-A2 antibodies for endothelial permeability

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Abstract

BACKGROUND:

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.

STUDY DESIGN AND METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

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