Adaptation of an amphibian mucociliary clearance model to evaluate early effects of tobacco smoke exposure.

RATIONALE: Inhaled side-stream tobacco smoke brings in all of its harmful components impairing mechanisms that protect the airways and lungs. Chronic respiratory health consequences are a complex multi-step silent process. By the time clinical manifestations require medical attention, several structural and functional changes have already occurred. The respiratory system has to undergo an iterative process of injury, healing and remodeling with every exposure. METHODS: To have a better understanding of the initial changes that take place when first exposed to environmental tobacco smoke, we have developed an exposure model, using the frog palate that closely represents the features of obstructive airways where ciliary dysfunction and mucus hypersecretion occur. RESULTS: Mucus transport was significantly reduced, even after exposure to the smoke of one cigarette (p < 0.05) and even further with 4-cigarettes exposure (p < 0.001). Morphometric and ultrastructural studies by SEM show extensive areas of tissue disruption. Gelatinase zymography shows activation of MMP9 in mucus from palates exposed to tobacco smoke. CONCLUSIONS: The clearance of mucus on the frog palate is significantly reduced after exposure to environmental tobacco smoke. Cilia and the extracellular matrix are anatomically disrupted. Tobacco smoke triggers an increased activity of matrix metalloproteinases associated with a substantial defoliation of ciliated epithelium. These studies enhance the knowledge of the changes in the mucociliary apparatus that occur initially after exposure to environmental tobacco smoke, with the goal of understanding how these changes relate to the genesis of chronic airway pathologies in humans.

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.

Evaluation of a mucoactive herbal drug, Radix Ophiopogonis, in a pathogenic quail model.

We investigated the effect of Radix Ophiopogonis on airway mucociliary clearance and mucus secretion in anesthetized quails. The oral administration of 10 g/kg of Radix Ophiopogonis significantly increased tracheal mucociliary transport velocity (MTV). Moreover, either 10 g/kg or 3 g/kg of Radix Ophiopogonis markedly attenuated the human neutrophil elastase (HNE)-induced decrease in MTV. Furthermore, we found that 10 g/kg of Radix Ophiopogonis significantly abolished the HNE-induced increases in fucose and protein contents of tracheal lavage, whereas Radix Ophiopogonis at the same dose only significantly decreased the protein content in the control group. These results suggest that Radix Ophiopogonis improves airway mucociliary clearance and that the improvement may, at least in part, be ascribed to the amelioration of airway mucus secretion.