Understanding effects of organic diesel exhaust particles. (Headliners: air pollution).

Numerous epidemiologic studies have shown that exposure to ambient particulate matter (PM) can exacerbate asthma and cause allergic inflammation. Diesel exhaust particles (DEPs)--an easily respirable component of PM--are known to cause proinflammatory effects in the respiratory tract. Although much is known about how DEPs affect macrophages, it is not known how the oxidative stress response differs between macrophages and epithelial cells, two primary cell targets of PM. New research by NIEHS grantee Andreas Nel and colleagues at the University of California at Los Angeles sheds light on these differences, as well as on mechanisms by which exposure to DEPs may adversely affect the respiratory system by inducing oxidative stress in bronchial epithelial cells.

DEPs consist of a carbonaceous core with a large surface area to which chemicals--including organic chemicals such as polycyclic aromatic hydrocarbons and their oxygenated derivatives--are absorbed. The researchers extracted organic chemicals from DEPs and applied them in culture to macrophages and bronchial epithelial cells. Then they compared the responses.

The researchers demonstrated that oxidative stress in epithelial cells caused the formation of heme oxygenase 1 and other markers. Although macrophages responded in a similar manner, epithelial cells produced more superoxide radicals and were more sensitive to cytotoxic effects resulting from mitochondrial damage, superoxide production, and energy depletion. In addition, the thiol antioxidant N-acetylcysteine protected macrophages against cytotoxic DEP chemicals but did not protect epithelial cells.

According to the researchers, these findings show that organic DEP chemicals induce a range of oxidative stress-related biological responses in epithelial cells and macrophages. They propose that this constitutes a stratified cellular response to oxidative stress, with the activation threshold for cellular injury requiring higher oxidative stress levels than those for cytoprotective responses. A stratified oxidative stress model in which biological end points are selected relevant to the level of oxidative stress and PM exposure may therefore prove useful in study of the adverse health effects of PM, they say.