Irritant-induced asthma to hypochlorite in mice due to impairment of the airway barrier

• Published in: Archives of toxicology Vol. 92; no. 4; pp. 1551 - 1561
• Main Authors: Van Den Broucke, Sofie, Pollaris, Lore, Vande Velde, Greetje, Verbeken, Erik, Nemery, Benoit, Vanoirbeek, Jeroen, Hoet, Peter
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2018; Springer Nature B.V
• Subjects: Alveoli; Asthma; Biomedical and Life Sciences; Biomedicine; Body weight; Breathing; Chlorine; Computed tomography; Denudation; Distilled water; Enlargement; Environmental Health; Exposure; Fuel consumption; Histology; Hypersensitivity; Image acquisition; Impairment; Inhalation; Leukocytes (eosinophilic); Leukocytes (neutrophilic); Lungs; Mice; Mineral oils; Naphthalene; Occupational Medicine/Industrial Medicine; Organ Toxicity and Mechanisms; Peritoneum; Permeability; Pharmacology/Toxicology; Proteins; Pulmonary functions; Respiration; Respiratory function; Respiratory tract; Airway epithelium; Airway damage; Irritants; Asthma
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-018-2161-8

Inhalation of commonly present irritants, such as chlorine and chlorine derivatives, can cause adverse respiratory effects, including irritant-induced asthma (IIA). We hypothesize that due to airway barrier impairment, exposure to hypochlorite (ClO - ) can result in airway hypersensitivity. C57Bl/6 mice received an intra-peritoneal (i.p.) injection of the airway damaging agent naphthalene (NA, 200 mg/kg body weight) or vehicle (mineral oil, MO). In vivo micro-computed tomography (CT) images of the lungs were acquired before and at regular time points after the i.p. treatment. After a recovery period of 14 days an intranasal (i.n.) challenge with 0.003% active chlorine (in ClO - ) or vehicle (distilled water, H 2 O) was given, followed by assessment of the breathing frequency. One day later, pulmonary function, along with pulmonary inflammation was determined. Lung permeability was assessed by means of total broncho-alveolar lavage (BAL) protein content and plasma surfactant protein (SP)-D levels. In vivo micro-CT imaging revealed enlargement of the lungs and airways early after NA treatment, with a return to normal at day 14. When challenged i.n. with ClO - , NA-pretreated mice immediately responded with a sensory irritant response. Twenty-four hours later, NA/ClO - mice showed airway hyperreactivity (AHR), accompanied by a neutrophilic and eosinophilic inflammation. NA administration followed by ClO - induced airway barrier impairment, as shown by increased BAL protein and plasma SP-D concentrations; histology revealed epithelial denudation. These data prove that NA-induced lung impairment renders the lungs of mice more sensitive to an airway challenge with ClO - , confirming the hypothesis that incomplete barrier repair, followed by irritant exposure results in airway hypersensitivity.