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

J Gustavo Zayas,Darryl W O'Brien,Shusheng Tai,Jie Ding,Malcolm King,Leonard Lim

doi:10.1186/1465-9921-5-9

Abstract

RationaleInhaled 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.MethodsTo 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.ResultsMucus 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.ConclusionsThe 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.

Highlights

Respiratory diseases, infectious and non-infectious, are a prime cause of morbidity, mortality and health system utilization in many countries
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
The clearance of mucus on the frog palate is significantly reduced after exposure to environmental tobacco smoke

Summary

Introduction

Respiratory diseases, infectious and non-infectious, are a prime cause of morbidity, mortality and health system utilization in many countries. Exposure to cigarette smoke is an important factor in causing as well as increasing complications in several pulmonary disorders. The mucociliary clearance constitutes the first line of defense to maintain the airways as free as possible of foreign bodies [1]. Respiratory Research 2004, 5:9 http://respiratory-research.com/content/5/1/9 of epithelial airway damage, ciliary dysfunction, inflammation, and change in mucus viscosity and/or elasticity. In laboratory studies we have shown that the physical properties of mucus in nonsmokers are not altered by age or by restrictive pulmonary pathology. Mucus properties show alterations when exposed to tobacco smoke and these alterations are noticeable in the very early stages of smoke exposure, even at an exposure level in the range of 1 to 5 cigarettes per day [2]

Results

Discussion

Conclusion