Oncotarget

Research Papers:

Neutrophil extracellular traps contribute to the pathogenesis of acid-aspiration-induced ALI/ARDS

Haitao Li, Xiaoting Zhou, Hongyi Tan, Yongbin Hu, Lemeng Zhang, Shuai Liu, Minhui Dai, Yi Li, Qian Li, Zhi Mao, Pinhua Pan _, Xiaoli Su and Chengpin Hu

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Oncotarget. 2018; 9:1772-1784. https://doi.org/10.18632/oncotarget.22744

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Abstract

Haitao Li1, Xiaoting Zhou2, Hongyi Tan3, Yongbin Hu4, Lemeng Zhang5, Shuai Liu1, Minhui Dai1, Yi Li1, Qian Li1, Zhi Mao1, Pinhua Pan1, Xiaoli Su1 and Chengpin Hu1

1Department of Pulmonary and Critical Care Medicine, Key Site of National Clinical Research Centre for Respiratory Disease, Xiangya Hospital, Central South University, Changsha 410008, China

2Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China

3Department of Respiratory Medicine, Changsha Central Hospital, Changsha, 410004, China

4Department of Pathological Medicine, Xiangya Hospital, Central South University, Changsha 410008, China

5Department of Thoracic Medicine, Hunan Cancer Hospital, Affiliated to Xiangya Medical School, Central South University, Changsha, 410013, China

Correspondence to:

Pinhua Pan, email: [email protected]

Keywords: neutrophil extracellular traps(NETs); acid-aspiration; acute lung injury(ALI); acute respiratory distress syndrome(ARDS)

Received: July 28, 2017     Accepted: October 30, 2017     Published: November 28, 2017

ABSTRACT

Background: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a manifestation of systemic inflammation in the lungs, but the factors that trigger inflammation in ALI/ARDS are unclear. We hypothesized that neutrophil extracellular traps (NETs) contribute to the pathogenesis of acid aspiration-induced ALI/ARDS.

Results: Analysis of bronchial aspirates from ARDS patients showed that NETs were significantly correlated with the degree of ARDS (r = –0.5846, p = 0.0359). NETs in bronchoalveolar lavage fluid of acid-aspiration mice were significantly higher (141.6 ± 23.08) at 3 h after injury than those in the sham group (1234 ± 101.9; p = 0.003, n = 5 per group). Exogenous NETs aggravated lung injury, while alvelestat and DNase markedly attenuated the intensity of ARDS.

Materials and Methods: We investigated whether NETs are involved in the severity of gastric aspiration-induced ARDS. Then, a hydrochloric acid aspiration-induced ALI murine model was used to assess whether NETs are pathogenic and whether targeting NETs is protective. Exogenous NETs were administered to mice. Alvelestat can inhibit neutrophil elastase (NE), which serves an important role in NET formation, so we investigated whether alvelestat could protect against ALI in cell and mouse models.

Conclusions: NETs may contribute to ALI/ARDS by promoting tissue damage and systemic inflammation. Targeting NETs by alvelestat may be a potential therapeutic strategy.


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