Journal article

Publication year: 2013

Pages: 2538-2548

Journal: Arteriosclerosis, Thrombosis, and Vascular Biology

Volume number: 33

Issue number: 11

ISSN: 1079-5642

eISSN: 1524-4636

Open access status: Bronze

DOI Link: https://doi.org/10.1161/ATVBAHA.113.301206

Publisher: American Heart Association

Abstract: 

Objective Antibodies against human neutrophil antigen-3a (HNA-3a) located on choline transporter-like protein 2 induce severe transfusion-related acute lung injury (TRALI). This study aims to identify the mechanism implicated in anti-HNA-3a-mediated TRALI.

Approach and Results Our analysis shows that anti-HNA-3a recognizes 2 choline transporter-like protein 2 isoforms (P1 and P2) on human microvascular endothelial cells from lung blood vessels but reacts only with the P1 isoform on neutrophils. Direct treatment of HNA-3a-positive endothelial cells with anti-HNA-3a, but not with anti-HNA-3b, leads to reactive oxygen species production, increased albumin influx, and decreased endothelial resistance associated with the formation of actin stress filaments and loosening of junctional vascular endothelium-cadherin. In a novel in vivo mouse model, TRALI was documented by significant increase in lung water content, albumin concentration, and neutrophil numbers in the bronchoalveolar lavage on injection of human anti-HNA-3a in lipopolysaccharides-treated, as well as nontreated mice. Interestingly, although neutrophil depletion alleviated severity of lung injury, it failed to prevent TRALI in this model. Infusion of anti-HNA-3a F(ab)(2) fragments caused moderate TRALI. Finally, mice lacking nicotinamide adenine dinucleotide phosphate oxidase (NOX2(y/-)) were protected from anti-HNA-3a-mediated TRALI.

Conclusions These data demonstrate the initiation of endothelial barrier dysfunction in vitro and in vivo by direct binding of anti-HNA-3a on endothelial cells. It seems, however, that the presence of neutrophils aggravates barrier dysfunction. This novel mechanism of TRALI primarily mediated by endothelial cell dysfunction via choline transporter-like protein 2 may help to define new treatment strategies to decrease TRALI-related mortality.

Harvard Citation style: Bayat, B., Tjahjono, Y., Sydykov, A., Werth, S., Hippenstiel, S., Weissmann, N., et al. (2013) Anti-Human Neutrophil Antigen-3a Induced Transfusion-Related Acute Lung Injury in Mice by Direct Disturbance of Lung Endothelial Cells, Arteriosclerosis, Thrombosis, and Vascular Biology, 33(11), pp. 2538-2548. https://doi.org/10.1161/ATVBAHA.113.301206

APA Citation style: Bayat, B., Tjahjono, Y., Sydykov, A., Werth, S., Hippenstiel, S., Weissmann, N., Sachs, U., & Santoso, S. (2013). Anti-Human Neutrophil Antigen-3a Induced Transfusion-Related Acute Lung Injury in Mice by Direct Disturbance of Lung Endothelial Cells. Arteriosclerosis, Thrombosis, and Vascular Biology. 33(11), 2538-2548. https://doi.org/10.1161/ATVBAHA.113.301206