Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Roles of reactive oxygen species and heme oxygenase-1 in modulation of alveolar macrophage-mediated pulmonary immune responses to listeria monocytogenes by diesel exhaust particles.

Authors
Yin-XJ; Ma-JYC; Antonini-JM; Castranova-V; Ma-JKH
Source
Toxicol Sci 2004 Nov; 82(1):143-153
NIOSHTIC No.
20025856
Abstract
Diesel exhaust particles (DEP) have been shown to suppress alveolar macrophage (AM)-mediated pulmonary immune responses to Listeria monocytogenes in vivo. In this study, effects of DEP-derived reactive oxygen species (ROS) and heme oxygenase (HO)-1 on AM-mediated immune responses to L. monocytogenes were investigated. Brown Norway rats were intratracheally inoculated with 100,000 L. monocytogenes, and AM were isolated at 7 days post-infection. Exposure to DEP or their organic extract (eDEP), but not the washed DEP (wDEP) or carbon black, increased intracellular ROS and HO-1 expression in AM. Induction of ROS and HO-1 by eDEP was partially reversed by alpha-naphthoflavone, a cytochrome P450 1A1 inhibitor, and totally blocked by N-acetylcysteine. In addition, exposure to eDEP, but not wDEP, inhibited lipopolysacchride-stimulated secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin-12 (IL-12), but augmented production of IL-10 by AM. Kinetic studies showed that modulation of cytokines by eDEP was preceded by ROS and HO-1 induction. Furthermore, pretreatment of AM with superoxide dismutase (SOD) or zinc protoporphrin IX (Znpp), which attenuated eDEP-induced HO-1 expression/activity, substantially inhibited eDEP effect on IL-10. Finally, direct stimulation with pyrogallol (PYR), a superoxide donor, upregulated HO-1 and IL-10 but decreased secretion of IL-12 in L. monocytogenes-infected AM. These results show that DEP, through eDEP-mediated ROS, induce HO-1 expression and IL-10 production and at the same time inhibit AM production of TNF-alpha and IL-12 to dampen the host immune responses. The results also suggest that HO-1 may play an important role in regulating production of IL-10 by DEP-exposed and L. monocytogenes-infected AM.
Keywords
Immune-reaction; Diesel-exhausts; Laboratory-animals; Animals; Animal-studies; Exposure-levels; Exposure-assessment; Pulmonary-function-tests; Particulates; In-vivo-study; Free-radicals
CODEN
TOSCF2
Publication Date
20041101
Document Type
Journal Article
Email Address
jma@hsc.wvu.edu
Fiscal Year
2005
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
1096-6080
NIOSH Division
HELD
Source Name
Toxicological Sciences
State
WV
TOP