ALTERATIONS IN SURFACTANT PROTEIN-A AFTER ACUTE EXPOSURE TO OZONE

The surfactant layer covering the gas-exchange region of the lung serv es as the initial site of interaction with inhaled oxidant gases. Amon g the endogenous compounds potentially vulnerable to oxidative injury are surfactant proteins. This study focused on the effect of ozone on surfactant protein A (SP-A) function, content, and gene expression. To determine the time course of response to ozone, guinea pigs were expo sed to 0.2-0.8 parts/million (ppm) ozone for 6 h and were killed up to 120 h postexposure. To determine the effect of repeated exposure, ani mals were exposed to 0.8 ppm ozone for 6 h/day and were killed on days 3 and 5. A significant increase in surfactant's ability to modulate t he respiratory burst induced by phorbol 12-myristate 13-acetate in nai ve macrophages was observed at 24 h after a single 0.8 ppm ozone expos ure. Because neutralizing antibodies to SP-A blunted this stimulatory effect, we hypothesized that ozone enhanced the modulatory role of SP- A in macrophage function. This alteration in function was accompanied by an influx of inflammatory cells and only marginal changes in SP-A l evels as determined by an enzyme-linked immunosorbent assay. No signif icant changes in steady-state levels of SP-A mRNA were observed after single or repeated exposure to ozone. Thus the inflammation that accom panies in vivo ozone exposure may result in a change in the structure and thus functional role of SP-A in modulating macrophage activity.