Editors' ChoiceLUNG INJURY

Casting a Wide NET for TRALI

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Science Translational Medicine  06 Jun 2012:
Vol. 4, Issue 137, pp. 137ec100
DOI: 10.1126/scitranslmed.3004398

Transfusion-related acute lung injury (TRALI) is the number one cause of transfusion-related mortality. Although the pathogenesis of TRALI is poorly understood, activation of neutrophils has been shown to cause severe damage to capillaries lining the lungs, which compromises lung function. To better understand this mechanism, Thomas et al. hypothesized that neutrophil extracellular traps, known as NETs, comprising DNA fibers coated with histones and antimicrobial proteins contribute to the development of TRALI.

Using fluorescence microscopy, the authors first showed that anti-neutrophil antibodies, such as antibody to HNA-3a, promoted NET formation by human neutrophils in vitro. This process was dependent on antibody–receptor (FcγRIIa) engagement. They further noted an increased presence of NETs in the plasma of mice with TRALI as compared with that of healthy control mice, by looking for higher levels of NET markers such as DNA, nucleosomes, and myeloperoxidase. Thomas and colleagues also directly visualized NET formation in the lungs of mice with TRALI (seen as DNA fibrous mesh coating the alveoli) using transmission electron microscopy and fluorescence microscopy. When mice were given the enzyme DNase I intranasally before TRALI induction or after the development of TRALI, they found that NET deposition in the lungs was prevented and that lung function improved, respectively. The authors also provided some evidence that NETs formed in patients who developed TRALI, although the increase in plasma levels of circulating DNA and nucleosomes that were observed could not be exclusively attributed to NET formation.

Thomas et al. provided convincing preliminary evidence in vitro and in an animal model that NETs play a role in the pathophysiology of TRALI. More studies are needed to definitively demonstrate the role of NET formation in humans, but by casting a wide net, the authors may have caught the first specific target for the prevention and treatment of TRALI.

G. M. Thomas et al., Extracellular DNA traps are associated with the pathogenesis of TRALI in humans and mice. Blood 17 May 2012 (10.1182/blood-2012-01-405183). [Abstract]

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