title: The cascade mechanism to explain ozone toxicity: the role of lipid ozonation products.
abstract: Ozone is so reactive that it can be predicted to be entirely consumed as it passes through the first layer of tissue it contacts at the lung/air interface. This layer includes the lung lining fluid (tracheobronchial surface fluid and alveolar and small airway lining fluid) and, where the lung lining fluid is thin or absent, the membranes of the epithelial cells that line the airways. Therefore, the biochemical changes that follow the inhalation of ozone must be relayed into deeper tissue strat by a cascade of ozonation products. Lipid ozonation products (LOP) are suggested to be the most likely species to act as signal transduction molecules. This is because unsaturated fatty acids are present in the lipids in both the lung lining fluid and in pulmonary cell bilayers, and ozone reacts with unsaturated fatty acids to produce ozone-specific products. Further, lipid ozonation products are finite in number, have structures that are predictable from the Criegee ozonation mechanism, and are small, diffusible, stable (or metastable) molecules. Preliminary data show that individual LOP cause the activation of specific lipases, which trigger the release of endogenous mediators of inflammation.
authors.affiliation: Biodynamics Institute, Louisiana State University, Baton Rouge, USA.
authors.forename: W A
authors.initials: WA
authors.lastname: Pryor
authors.forename: G L
authors.initials: GL
authors.lastname: Squadrito
authors.forename: M
authors.initials: M
authors.lastname: Friedman
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005609:Free Radicals; D006801:Humans; D050356:Lipid Metabolism; D008081:Liposomes / Q000378:metabolism; D008954:Models, Biological; D010126:Ozone / Q000378:metabolism* / Q000633:toxicity*
chemical_list: D005609:Free Radicals; D008081:Liposomes; D010126:Ozone