Effects of cadmium on E-cadherin and VE-cadherin in mouse lung.
Exposure to Cd(2+) via inhalation or intratracheal instillation results in pulmonary edema, which is followed by the influx of leukocytes, the proliferation of type II pneumocytes and eventual scarring and fibrotic changes. While the general toxic effects of Cd(2+) in the lung have been well characterized, the specific molecular mechanisms underlying these effects have yet to be elucidated. Previously we have shown that Cd(2+) can disrupt the adhering junctions between various types of epithelial and endothelial cells in culture, most likely by perturbing the function of the Ca(2+) dependent cell adhesion molecules E-cadherin and VE-cadherin respectively. The objectives of this study were to determine whether respiratory exposure to Cd(2+) can alter the localization of E-cadherin and VE-cadherin in the lung, and to determine whether this effect may play a role in the acute pneumotoxic response to Cd(2+). Male CF-1 mice were exposed to CdCl(2) (0, 16.25, 32.5, 65 or 130 nmoles in 50 microl saline) via intratracheal instillation. After 24 hours, the lungs were removed and either subjected to bronchoalveolar lavage or analyzed for histopathologic changes. The results showed that Cd(2+) caused an increase in lung weight and in the protein content of the lavage fluid. These effects were accompanied by a pronounced decrease in the amount of E-cadherin in epithelial cells of the alveoli and small bronchioles and of VE-cadherin in vascular endothelial cells. Assessment of cell membrane integrity with ethidium homodimer-1 showed no evidence of severe injury or death in alveolar epithelial cells. These findings suggest that E-cadherin and VE-cadherin may be important early targets of Cd(2+) toxicity in the lung.
Pearson
Celeste A
CA
Department of Pharmacology, Midwestern University, 555 31st Street, Downers Grove, IL 60515, USA.
Lamar
Peter C
PC
Prozialeck
Walter C
WC
D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000032:analysis*; D002104:Cadmium / Q000633:toxicity*; D002463:Cell Membrane Permeability; D004847:Epithelial Cells / Q000378:metabolism; D007150:Immunohistochemistry; D008168:Lung / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D002104:Cadmium; D000099152:Cadherin 5