A new mechanism for the toxicity of ozone.

Ozone, with its high reactivity, is entirely consumed as it passes through 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 inhalation of ozone must be relayed into deeper tissue strata by a cascade of ozonation products. Lipid ozonation products (LOP) are suggested to be the most likely relay molecules of ozone's signal. This is because unsaturated fatty acids are present in relatively high concentrations in both the ELF and in pulmonary cell bilayers, and ozone reacts with unsaturated fatty acids to produce ozone-specific products. Further, LOP are finite in number, have structures that are predictable from the Criegee ozonation mechanism, and are small, diffusible, stable (or meta-stable) molecules, similar to other lipid-derived signal transduction species. Preliminary data show that individual LOP cause the activation of specific lipases, which trigger the release of endogenous mediators of inflammation.