Mengling Xia1, Fei Xu1, Hangqi Ni1, Qing Wang1, Ruhui Zhang1, Yafang Lou2, Jianying Zhou3. 1. Department of Respiratory Disease, Thoracic Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79, Qingchun Road, 310003, Hangzhou, China. 2. Department of Respiratory Medicine, Hangzhou Hospital of Traditional Chinese Medicine, No. 453, Tiyuchang Road, 310013, Hangzhou, China. louyafang18@126.com. 3. Department of Respiratory Disease, Thoracic Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79, Qingchun Road, 310003, Hangzhou, China. zjyhz@zju.edu.cn.
Abstract
BACKGROUND: Asthma is one of the most common chronic diseases that affects more than 300 million people worldwide. Though most asthma can be well controlled, individuals with severe asthma experience recurrent exacerbations and impose a substantial economic burden on healthcare system. Neutrophil inflammation often occurs in patients with severe asthma who have poor response to glucocorticoids, increasing the difficulty of clinical treatment. METHODS: We established several neutrophil-dominated allergic asthma mouse models, and analyzed the airway hyperresponsiveness, airway inflammation and lung pathological changes. Neutrophil extracellular traps (NETs) formation was analyzed using confocal microscopy and western blot. RESULTS: We found that the ovalbumin (OVA)/complete Freund's adjuvant (CFA)/low-dose lipopolysaccharide (LPS)-induced mouse model best recapitulated the complex alterations in the airways of human severe asthmatic patients. We also observed OVA/CFA/LPS-exposed mice produced large quantities of neutrophil extracellular traps (NETs) in lung tissue and bone marrow neutrophils. Furthermore, we found that reducing the production of NETs or increasing the degradation of NETs can reduce airway inflammation and airway hyperresponsiveness. CONCLUSION: Our findings identify a novel mouse model of neutrophilic asthma. We have also identified NETs play a significant role in neutrophilic asthma models and contribute to neutrophilic asthma pathogenesis. NETs may serve as a promising therapeutic target for neutrophilic asthma.
BACKGROUND: Asthma is one of the most common chronic diseases that affects more than 300 million people worldwide. Though most asthma can be well controlled, individuals with severe asthma experience recurrent exacerbations and impose a substantial economic burden on healthcare system. Neutrophil inflammation often occurs in patients with severe asthma who have poor response to glucocorticoids, increasing the difficulty of clinical treatment. METHODS: We established several neutrophil-dominated allergic asthma mouse models, and analyzed the airway hyperresponsiveness, airway inflammation and lung pathological changes. Neutrophil extracellular traps (NETs) formation was analyzed using confocal microscopy and western blot. RESULTS: We found that the ovalbumin (OVA)/complete Freund's adjuvant (CFA)/low-dose lipopolysaccharide (LPS)-induced mouse model best recapitulated the complex alterations in the airways of human severe asthmatic patients. We also observed OVA/CFA/LPS-exposed mice produced large quantities of neutrophil extracellular traps (NETs) in lung tissue and bone marrow neutrophils. Furthermore, we found that reducing the production of NETs or increasing the degradation of NETs can reduce airway inflammation and airway hyperresponsiveness. CONCLUSION: Our findings identify a novel mouse model of neutrophilic asthma. We have also identified NETs play a significant role in neutrophilic asthma models and contribute to neutrophilic asthma pathogenesis. NETs may serve as a promising therapeutic target for neutrophilic asthma.
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