The surfactant layer covering the gas-exchange region of the lung serves as the initial site of interaction with inhaled oxidant gases. Among 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 exposed 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, animals 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 the respiratory burst induced by phorbol 12-myristate 13-acetate in naive macrophages was observed at 24 h after a single 0.8 ppm ozone exposure. 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 levels as determined by an enzyme-linked immunosorbent assay. No significant changes in steady-state levels of SP-A mRNA were observed after single or repeated exposure to ozone. Thus the inflammation that accompanies in vivo ozone exposure may result in a change in the structure and thus functional role of SP-A in modulating macrophage activity.
Role of surfactant protein A in non-infectious lung diseases