Airway Permeability in Rats Exposed to Ozone or Treated with Cytoskeleton-Destabilizing Drugs

Abstract

Ozone (OJ exposure of rats increases airway epithelial permeability. We hypothesized that this increased permeability may be mediated by the epithelial cell cytoskeleton. To test this hypothesis, we studied the effect of cytoskeletal disruption on the transmucosal transport of tracers from airway lumen to blood and compared the results with the effects of O₂) exposure. No increase in transport occurred following disruption of microtubules by vinblastine, but disruption of microfilaments with cytochalasin D resulted in increased transport of radiolabeled tracers f^Tc- and ^1UIn-labeled diethylenetriamine-pentacetate (DTPA) and ¹²⁵I-labeled bovine serum albumin (BSA)] In control rats, both horseradish peroxidase (HRP) and BSA, localized by cytochemistry and autoradiography, respectively, were detected on the epithelial cell surfaces and in endocytic vesicles. In rats treated with cytochalasin D or exposed to Oj, the tracer molecules also penetrated the intercellular spaces, though the apical tight junctions remained devoid of the tracers. Increased numbers of endocytic vesicles containing HRP and aggregation of^mI-labeled BSA autoradiographic grains in the subepithelial region were also seen after either treatment. We conclude that destabilization of cytoskeletal elements following 0₂) exposure is a possible mechanism of increased transmucosal transport, which may be a combined effect of accelerated transport through both endocytic and paracellular pathways.