Anti–Human Neutrophil Antigen-3a Induced Transfusion-Related Acute Lung Injury in Mice by Direct Disturbance of Lung Endothelial Cells

• DOI: 10.1161/atvbaha.113.301206
• Publication Date: 2013-09-06T04:02:18Z
• Authors: Behnaz Bayat; Yudy Tjahjono; Akylbek Sydykov; Silke Werth; Stefan Hippenstiel; Nobert Weissmann; Ulrich J. Sachs; Sentot Santoso
• Keywords: Neutrophil Extracellular Traps

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.Our analysis shows that anti-HNA-3a recognizes isoforms (P1 and P2) microvascular endothelial cells from blood vessels but reacts only with P1 isoform neutrophils. Direct treatment of HNA-3a-positive anti-HNA-3a, not anti-HNA-3b, leads reactive oxygen species production, increased albumin influx, decreased resistance associated formation actin stress filaments loosening junctional vascular endothelium-cadherin. In a novel vivo mouse model, TRALI was documented by significant increase water content, concentration, numbers bronchoalveolar lavage injection lipopolysaccharides-treated, as well nontreated mice. Interestingly, although depletion alleviated severity injury, it failed prevent this model. Infusion F(ab')2 fragments caused moderate TRALI. Finally, mice lacking nicotinamide adenine dinucleotide phosphate oxidase (NOX2(y/-)) were protected TRALI.These data demonstrate initiation barrier dysfunction vitro direct binding cells. It seems, however, presence neutrophils aggravates dysfunction. primarily mediated cell via may help define new strategies decrease TRALI-related mortality.