A mechanism of airway injury in an epithelial model of mucociliary clearance.
We studied the action of sodium metabisulphite on mucociliary transport in a frog palate epithelial injury model, hypothesizing that it may be useful for the study of mechanisms of airway injury. Sodium metabisulphite (MB) releases SO2 on contact with water. SO2 is a pollutant in automobile fumes and may play a role in the exacerbation of airway disease symptoms. We first investigated its effect on mucociliary clearance. MB 10(-1) M, increased mucociliary clearance time (MCT) by 254.5 +/- 57.3% of control values, (p < 0.001, n = 7). MB 10(-4) and 10(-2) M did not interfere with mucus clearance time compared to control values. In MB-treated frog palates, MCT did not return to control values after one hour (control, 97.3 +/- 6.3% vs. MB, 140.9 +/- 46.3%, p < 0.001, n = 7). Scanning EM images of epithelial tissue were morphometrically analyzed and showed a 25 +/- 12% loss of ciliated cells in MB palates compared to controls with an intact ciliary blanket. Intact cells or groups of ciliated cells were found in scanning EM micrographs of mucus from MB-treated palates. This was associated with increased matrix metalloproteinase (MMP-9) activity in epithelial tissue and mucus. We suggest that the loss of ciliated cells as a result of MMP-9 activation prevented full recovery of MCT after MB 10(-1) M. The mechanism of action may be on epithelial cell-cell or cell-matrix attachments leading to cell loss and a disruption of MCT. Further studies are warranted to determine whether this is an inflammatory mediated response or the result of a direct action on epithelial cells and what role this mechanism may play in the progression to chronic airway diseases with impaired mucociliary clearance.
O'Brien
Darryl W
DW
Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. do1@ualberta.ca <do1@ualberta.ca>
Morris
Melanie I
MI
Ding
Jie
J
Zayas
J Gustavo
JG
Tai
Shusheng
S
King
Malcolm
M
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008171:Lung Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009079:Mucociliary Clearance / Q000187:drug effects*; D010159:Palate / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D011892:Rana catesbeiana; D020545:Respiratory Mucosa / Q000187:drug effects / Q000473:pathology; D013447:Sulfites / Q000008:administration & dosage*
D013447:Sulfites; C005200:sodium metabisulfite; D020782:Matrix Metalloproteinases