A NEW MECHANISM FOR THE TOXICITY OF OZONE

Ozone, with its high reactivity, is entirely consumed as it passes thr ough the first layer of tissue it contacts at the lung/air interface. This layer includes the epithelial cell lining fluid (ELF) and, where the ELF is thin or absent, the membranes of the epithelial cells that line the airways. Thus the biochemical changes that follow the inhalat ion of ozone must be relayed into deeper tissue strata by a cascade of ozonation products. Lipid ozonation products (LOP) are suggested to b e the most likely relay molecules of ozone's signal. This is because u nsaturated fatty acids are present in relatively high concentrations i n both the ELF and in pulmonary cell bilayers, and ozone reacts with u nsaturated fatty acids to produce ozone-specific products. Further, LO P are finite in number, have structures that are predictable from the Criegee ozonation mechanism, and are small, diffusible, stable (or met a-stable) molecules, similar to other lipid-derived signal transductio n species. Preliminary data show that individual LOP cause the activat ion of specific lipases, which trigger the release of endogenous media tors of inflammation.