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Roles of reactive oxygen species, HEME oxygenase-1, and nitric oxide in diesel exhaust particle-mediated pulmonary immune responses to listeria monocytogenes in rats.

Yin-X; Ma-J; Antonini-J; Ma-J
Toxicologist 2003 Mar; 72(S-1):375
This study examines the hypothesis that diesel exhaust particles (DEP) suppress pulmonary immunity to Listeria monocytogenes (Listeria) through the induction of reactive oxygen species (ROS), heme oxygenase-1 (HO-1) and altered cytokine production by alveolar macrophages (AM) and lymphocytes. Cells were isolated from Brown Norway rats intratracheally inoculated with saline or 100,000 Listeria at 7 days post-infection. The Listeria-infected AM showed increased production of IL-6, IL-10, IL-12, and TNF-alpha over the saline control in response to lipopolysacchride (LPS), whereas the Listeria-infected lymphocytes showed increased production of IL-2, IL-10, and IFN-gamma when challenged with concanavalin A (ConA) or heat killed Listeria (HKLM). DEP or DEP extract, but not the washed DEP, inhibited AM secretion of IL-6, IL-12, and TNF-alpha and lymphocyte production of IL-2 and IFN-gamma, but enhanced AM production of IL-10. The effect of the DEP extract on cytokine production was preceded by a time-dependent induction of ROS and ROS-induced HO-1 protein and activity in AM. alpha-Naphthoflavone (ANF), a CYP 1A1 inhibitor, partially inhibited DEP-induced ROS and HO-1 expression and reversed the DEP effect on cytokine secretion. L-NAME (N-nitro-L-arginine methyl ester), a NO synthase inhibitor, inhibited the DEP-induced ROS generation and HO-1 induction, but augmented the DEP-induced IL-10 production by Listeria-infected AM, suggesting that NO down-regulates IL-10 production. Similar to DEP extract, hemin induced HO-1 expression, an increase in IL-10 and a decrease in TNF-alpha production by AM. In comparison, DEP extract at a level that induced less HO-1 than hemin, showed greater effect on IL-10 secretion. These results show that both HO-1 and NO play a role in AM production of IL-10, and that due to its organic content, DEP suppress the host immune responses by inhibiting the innate and T cell-mediated immunity and augmenting AM production of IL-10 (NIH HL-62630).
Diesel-exhausts; Particulate-dust; Particulates; Dusts; Pulmonary-system; Lymphocytes; Laboratory-animals; Animal-studies; Animals; Combustion-gases; Combustion-products
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Priority Area
Work Environment and Workforce: Mixed Exposures
Source Name
The Toxicologist. Society of Toxicology 42nd Annual Meeting and ToxExpo, Cutting-Edge Science, Networking, New Perspectives, March 9-13, 2003, Salt Lake City, Utah