Time course of airway remodelling after an acute chlorine gas exposure in mice.
Accidental chlorine (Cl2) gas inhalation is a common cause of acute airway injury. However, little is known about the kinetics of airway injury and repair after Cl2 exposure. We investigated the time course of airway epithelial damage and repair in mice after a single exposure to a high concentration of Cl2 gas. Mice were exposed to 800 ppm Cl2 gas for 5 minutes and studied from 12 hrs to 10 days post-exposure. The acute injury phase after Cl2 exposure (< or = 24 hrs post-exposure) was characterized by airway epithelial cell apoptosis (increased TUNEL staining) and sloughing, elevated protein in bronchoalveolar lavage fluid, and a modest increase in airway responses to methacholine. The repair phase after Cl2 exposure was characterized by increased airway epithelial cell proliferation, measured by immunoreactive proliferating cell nuclear antigen (PCNA), with maximal proliferation occurring 5 days after Cl2 exposure. At 10 days after Cl2 exposure the airway smooth muscle mass was increased relative to controls, suggestive of airway smooth muscle hyperplasia and there was evidence of airway fibrosis. No increase in goblet cells occurred at any time point. We conclude that a single exposure of mice to Cl2 gas causes acute changes in lung function, including pulmonary responsiveness to methacholine challenge, associated with airway damage, followed by subsequent repair and airway remodelling.
Tuck
Stephanie A
SA
Meakins-Christie Laboratories, McGill University, Montreal, Canada. stephanie_tuck@hotmail.com
Ramos-Barbón
David
D
Campbell
Holly
H
McGovern
Toby
T
Karmouty-Quintana
Harry
H
Martin
James G
JG
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001249:Asthma / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects*; D002713:Chlorine / Q000633:toxicity*; D004195:Disease Models, Animal; D005740:Gases / Q000633:toxicity*; D020397:Goblet Cells / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D016210:Methacholine Chloride; D051379:Mice; D018809:Proliferating Cell Nuclear Antigen / Q000187:drug effects; D023382:Toxicity Tests, Acute
D005740:Gases; D018809:Proliferating Cell Nuclear Antigen; D016210:Methacholine Chloride; D002713:Chlorine