Acute lung injury induced by chlorine inhalation in C57BL/6 and FVB/N mice.
Humans may be exposed to chlorine gas via accidental or intentional release, and effective countermeasures for the resulting lung injury are lacking. To develop a model in which therapeutic measures could be evaluated, lung injury induced by chlorine inhalation in two inbred mouse strains was examined. C57BL/6 and FVB/N mice were exposed for 1.1 h to varying doses of chlorine (197-289 ppm-h) and were evaluated for indices of lung injury at different times after exposure (6-48 h). Chlorine induced increases in lung weight that were more evident in FVB/N mice than in C57BL/6 mice. Both strains exhibited sloughing of airway epithelium observed within 6 h after exposure. As judged by Ly-6G immunostaining, chlorine exposure caused widespread neutrophil influx into the lung parenchyma at 6 h followed by a clustering of neutrophils around damaged airways by 24 h. High levels of cellular proliferation revealed by Ki-67 staining were observed in airway epithelium 48 h after exposure. Lavage fluid parameters showed consistent trends in both strains. Lavage fluid protein content was elevated throughout the times examined. Lavage fluid neutrophils were significantly increased beginning 12 h after exposure and were highest at 48 h. The concentration of the neutrophil chemoattractant KC peaked 6 h after exposure and was near baseline by 48 h. In summary, chlorine inhalation resulted in lung injury characterized by edema, epithelial cell death, and neutrophilic inflammation in C57BL/6 and FVB/N mice. Characterization of such responses in these mice will allow testing of therapeutic agents to treat chlorine-induced lung injury.
Tian
Xiaohua
X
Section of Pulmonary Diseases, Critical Care and Environmental Medicine, Department of Medicine, Tulane University Health Sciences Center, Louisiana, USA.
Tao
Hui
H
Brisolara
Joseph
J
Chen
Jing
J
Rando
Roy J
RJ
Hoyle
Gary W
GW
D000208:Acute Disease; D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D049109:Cell Proliferation / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000633:toxicity*; D054371:Chemokine CXCL11 / Q000032:analysis; D002713:Chlorine / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011506:Proteins / Q000032:analysis; D020545:Respiratory Mucosa / Q000187:drug effects; D013045:Species Specificity
D002619:Chemical Warfare Agents; D054371:Chemokine CXCL11; D011506:Proteins; D002713:Chlorine