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Neutrophils Mediate Airway Hyperresponsiveness after Chlorine-Induced Airway Injury in the Mouse
- Source :
- American Journal of Respiratory Cell and Molecular Biology. 52:513-522
- Publication Year :
- 2015
- Publisher :
- American Thoracic Society, 2015.
-
Abstract
- Chlorine gas (Cl2) inhalation causes oxidative stress, airway epithelial damage, airway hyperresponsiveness (AHR), and neutrophilia. We evaluated the effect of neutrophil depletion on Cl2-induced AHR and its effect on the endogenous antioxidant response, and if eosinophils or macrophages influence Cl2-induced AHR. We exposed male Balb/C mice to 100 ppm Cl2 for 5 minutes. We quantified inflammatory cell populations in bronchoalveolar lavage (BAL), the antioxidant response in lung tissue by quantitative PCR, and nuclear factor (erythroid-derived 2)-like 2 (NRF2) nuclear translocation by immunofluorescence. In vitro, NRF2 nuclear translocation in response to exogenous hypochlorite was assessed using a luciferase assay. Anti-granulocyte receptor-1 antibody or anti-Ly6G was used to deplete neutrophils. The effects of neutrophil depletion on IL-13 and IL-17 were measured by ELISA. Eosinophils and macrophages were depleted using TRFK5 or clodronate-loaded liposomes, respectively. AHR was evaluated with the constant-phase model in response to inhaled aerosolized methacholine. Our results show that Cl2 exposure induced neutrophilia and increased expression of NRF2 mRNA, superoxide dismutase-1, and heme-oxygenase 1. Neutrophil depletion abolished Cl2-induced AHR in large conducting airways and prevented increases in antioxidant gene expression and NRF2 nuclear translocation. Exogenous hypochlorite administration resulted in increased NRF2 nuclear translocation in vitro. After Cl2 exposure, neutrophils occupied 22 ± 7% of the luminal space in large airways. IL-17 in BAL was increased after Cl2, although this effect was not prevented by neutrophil depletion. Neither depletion of eosinophils nor macrophages prevented Cl2-induced AHR. Our data suggest the ability of neutrophils to promote Cl2-induced AHR is dependent on increases in oxidative stress and occupation of luminal space in large airways.
- Subjects :
- Male
Pulmonary and Respiratory Medicine
medicine.medical_specialty
NF-E2-Related Factor 2
Neutrophils
Clinical Biochemistry
Active Transport, Cell Nucleus
Endogeny
Biology
medicine.disease_cause
chemistry.chemical_compound
Internal medicine
Gene expression
medicine
Animals
Asthma, Occupational
Lung
Molecular Biology
Mice, Inbred BALB C
medicine.diagnostic_test
Superoxide
Cell Biology
respiratory system
Molecular biology
Neutrophilia
Up-Regulation
respiratory tract diseases
Oxidative Stress
Bronchoalveolar lavage
Endocrinology
chemistry
biology.protein
Cytokines
Methacholine
Chlorine
Clodronic Acid
medicine.symptom
Antibody
Oxidative stress
Granulocytes
medicine.drug
Subjects
Details
- ISSN :
- 15354989 and 10441549
- Volume :
- 52
- Database :
- OpenAIRE
- Journal :
- American Journal of Respiratory Cell and Molecular Biology
- Accession number :
- edsair.doi.dedup.....48c3b6f33991b3d4593de1d131b77316