Alteration of epithelial integrity, alkaline phosphatase activity, and fibronectin expression in lungs of rats exposed to ozone

The deleterious effects of ozone (O-3), an oxidant air pollutant, in the lu ng are dependent on dose and exposure duration and generally evolve with ti me postexposure. This study characterized the time sequence of epithelial i njury and fibronectin expression in the lungs of rats exposed to O-3. Bronc hoalveolar lavage (BAL) fluid was analyzed for alkaline phosphatase and tot al protein as markers of epithelial injury and increased permeability, and fibronectin for its role in inflammation and lung injury. The results revea led a time-related increase in total protein in the BAL fluid following a 3 -h exposure of rats to I ppm O-3. The increased protein concentrations peak ed at 12 h and then declined but remained significantly higher than control at 24 h postexposure. A similar time-related significant increase also occ urred for BAL fibronectin and alkaline phosphatase activity. However, the r eturn of alkaline phosphatase levels to baseline prior to a comparable redu ction in protein levels suggests repair of injured cells, but a delay in th e formation of epithelial junctions that limit the transfer of serum protei ns to air spaces. By cytochemistry, alkaline phosphatase activity was detec ted in association with lung type II epithelial cells and in BAL polymorpho nuclear leukocytes (PMNs), but not in macrophages. While a significant incr ease in cytochemically detectable alkaline phosphatase resulted from the in crease in PMN number following O-3 exposure, mononuclear cells constituted the primary cell type responsible for fibronectin mRNA upregulation. While the cytochemical observations support the role of inflammatory cells in the injury process, the comparability of temporal changes in BAL protein, fibr onectin, and alkaline phosphatase suggests a mechanistic role for fibronect in in lung injury.