Interactive Effects of O3, Cytochalasin D, and Vinblastine on Transepithelial Transport and Cytoskeleton in Rat Airways

Cytoskeletal perturbations and associated changes in transepithelial transport in rat airways were analyzed after in vivo treatment with cytochalasin D or vinblastine or exposure to ozone (O3). Exposure of O3 or cytochalasin D, but not vinblastine, increased permeability in the bronchoalveolar region. Combined treatment with cytochalasin D and O3 did not increase the effect seen with each agent alone. However, treatment with vinblastine plus 0.8 ppm O3 resulted in a slight enhancement of permeability over that seen with O3 alone. This enhancement was not seen with 2 ppm O3. When cytochalasin and vinblastine treatment were combined, a synergistic effect on bronchoalveolar permeability was seen, suggesting participation of both microfilamentous and microtubular cytoskeletal elements in maintaining the integrity of the bronchoalveolar epithelium. Potentially harmful effects of O3 on cytoskeletal elements were confirmed in rat lung epithelial cells in culture. O3 exposure produced reversible changes in microfilamentous structures comparable to those produced by cytochalasin D. The results of these studies support the hypotheses that the cytoskeleton has a central role in maintenance of respiratory epithelial integrity and that a target for O3 toxicity may be the components of cytoskeleton. These results, however, do not rule out the possibility that treatment with cytoskeleton destabilizing drugs leads to the release of mediators, which in turn contribute to the airway epithelial dysfunction and increased permeability.