Tracheal permeability in rats exposed to ozone. An electron microscopic and autoradiographic analysis of the transport pathway.

Abstract

Exposure of rats to ozone (O3), 0.8 ppm increases the tracheal permeability to 99mTc-diethylenetriaminepentaacetate (99mTc-DTPA) about twofold but to 125I-bovine serum albumin (125I-BSA) to a lesser extent. It is generally believed that exposure to air pollutants causes perturbation of tight junctions and formation of intercellular channels for the passage of molecules from airway lumen to blood. We now report that a second mechanism, vesicular transport, is operative in the transepithelial movement of molecules, that this mechanism is speeded in tracheas of O3-exposed rats, and that there is a concurrent delay in movement of BSA from connective tissue to capillaries after O3 exposure. Horseradish peroxidase (HRP) instilled in trachea was taken up by endocytic vesicles, which could be localized in apical as well as basal regions of ciliated and nonciliated cells. A count of HRP-positive vesicles and measurement of their surface area revealed an approximate twofold increase in O3-exposed rats over that in control animals breathing clean air; this paralleled a twofold increase in transport of 99mTc-DTPA from tracheal lumen to blood. An autophagocytic process induced in tracheal epithelial cells by O3 is proposed. Despite the difference in the size of HRP and BSA, the 2 molecules migrated through common pathways and were colocalized in the luminal membranes as well as in endocytic vesicles and intercellular spaces in double labeling experiments involving simultaneous detection of HRP by cytochemistry and 125I-BSA by autoradiography. This procedure proved particularly useful in detecting a dramatic accumulation of 125I-BSA autoradiographic grains in subepithelial connective tissue and HRP accumulation in intercellular spaces and at the basal membrane-connective tissue junction in O3-exposed rats.(ABSTRACT TRUNCATED AT 250 WORDS)