Roles of Reactive Oxygen Species, HEME Oxygenase-1, and Nitric Oxide in Diesel Exhaust Particle-Mediated Pulmonary Immune Responses to Listeria monocytogenes in Rats

Details

• Personal Author:
  Antonini J ; Ma J ; Yin X
• Description:
  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). [Description provided by NIOSH]
• Subjects:
  Animals Blood Dust Laboratories Lung Occupational Health Particulate Matter Respiratory System Safety Vehicle Emissions
• Keywords:
  Animal-studies Combustion-gases Combustion-products Diesel-exhausts Dusts Laboratory-animals Lymphocytes Particulate-dust Particulates Pulmonary-system
• ISSN:
  1096-6080
• Publisher:
  Society of Toxicology
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  72
• NIOSHTIC Number:
  nn:20022701
• Citation:
  Toxicologist 2003 Mar; 72(S-1):375
• Federal Fiscal Year:
  2003
• NORA Priority Area:
  Work Environment and Workforce: Mixed Exposures
• Peer Reviewed:
  False
• Source Full 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
• Supplement:
  1
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:000f0aa53dd394a2cdda104e88b9c3ebaebef3bf1ccbdc7836d1b18e99b69a70c23567fb0ad44f651370eeaffa2158fbc8a4b376d83409f760f9bb010564f583
• Download URL:
  https://stacks.cdc.gov/view/cdc/199383/cdc_199383_DS1.pdf
• File Type:
  [PDF - 56.71 KB ]