Wa. Pryor et al., THE CASCADE MECHANISM TO EXPLAIN OZONE TOXICITY - THE ROLE OF LIPID OZONATION PRODUCTS, Free radical biology & medicine, 19(6), 1995, pp. 935-941
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 (tracheobron
chial surface fluid and alveolar and small ah-way lining fluid) and, w
here the lung lining fluid is thin or absent, the membranes of the epi
thelial cells that line the airways. Therefore, the biochemical change
s that follow the inhalation of ozone must be relayed into deeper tiss
ue strata by a cascade of ozonation products. Lipid ozonation products
(LOP) are suggested to be the most likely species to act as signal tr
ansduction molecules. This is because unsaturated fatty acids are pres
ent in the lipids in both the lung lining fluid and in pulmonary cell
bilayers, and ozone reacts with unsaturated fatty acids to produce ozo
ne-specific products. Further, lipid ozonation products are finite in
number, have structures that are predictable from the Criegee ozonatio
n mechanism, and are small, diffusible, stable (or metastable) molecul
es. Preliminary data show that individual LOP cause the activation of
specific lipases, which trigger the release of endogenous mediators of
inflammation.