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Title: Organic extract of diesel exhaust particles stimulates expression of Ia and costimulatory molecules associated with antigen presentation in rat peripheral blood monocytes but not in alveolar macrophages

Abstract

We hypothesized that diesel exhaust particles (DEP) induce the activation of antigen-presenting cells (APC) in lung. The present study was designed to clarify the following about DEP: (1) whether it affects the expression of Ia and B7 molecules in alveolar macrophages (AM) as a mature cell or in peripheral blood monocytes (PBM) as an immature cell (2) if it affects the antigen-presenting (AP) activity of PBM (3) what component of DEP is responsible for the effects, and (4) whether the effect of DEP is related to oxidative stress. DEP was extracted with methylene chloride. Cells were exposed to whole DEP, organic extract, or residual particles for 24 h. Cell-surface molecules were measured by flow cytometry. AP activity was assessed by antigen-specific T cell proliferation. Whole DEP or organic extract significantly increased the expression of Ia and B7 molecules on PBM but not on AM. No significant effect of residual particles was observed. A low concentration of organic extract also increased the AP activity of PBM. When the induction of an antioxidative enzyme was assessed, heme oxygenase-1 protein was found to be significantly increased by exposure to whole DEP, and the organic extract was more effective than the residual particles. Furthermore,more » the organic extract-induced expression of Ia antigen on PBM was reduced by the addition of an antioxidative agent. These results suggest that DEP may act on immature APC and enhance their AP activity and that the action contributing to oxidative stress may be mediated by organic compounds of DEP.« less

Authors:
 [1];  [2]
  1. Particulate Matter (PM2.5) and Diesel Exhaust Particles (DEP) Research Project, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506 (Japan). E-mail: ekoike@nies.go.jp
  2. Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506 (Japan)
Publication Date:
OSTI Identifier:
20783392
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 209; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2005.04.017; PII: S0041-008X(05)00189-4; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CATTLE; CYSTEINE; DEOXYURIDINE; DMSO; HEME; HISTOCOMPATIBILITY COMPLEX; MACROPHAGES; METHYLENE CHLORIDE; MONOCYTES; OVALBUMIN; PENICILLIN; POLYCYCLIC AROMATIC HYDROCARBONS; RATS; STREPTOMYCIN

Citation Formats

Koike, Eiko, and Kobayashi, Takahiro. Organic extract of diesel exhaust particles stimulates expression of Ia and costimulatory molecules associated with antigen presentation in rat peripheral blood monocytes but not in alveolar macrophages. United States: N. p., 2005. Web. doi:10.1016/j.taap.2005.04.017.
Koike, Eiko, & Kobayashi, Takahiro. Organic extract of diesel exhaust particles stimulates expression of Ia and costimulatory molecules associated with antigen presentation in rat peripheral blood monocytes but not in alveolar macrophages. United States. doi:10.1016/j.taap.2005.04.017.
Koike, Eiko, and Kobayashi, Takahiro. Thu . "Organic extract of diesel exhaust particles stimulates expression of Ia and costimulatory molecules associated with antigen presentation in rat peripheral blood monocytes but not in alveolar macrophages". United States. doi:10.1016/j.taap.2005.04.017.
@article{osti_20783392,
title = {Organic extract of diesel exhaust particles stimulates expression of Ia and costimulatory molecules associated with antigen presentation in rat peripheral blood monocytes but not in alveolar macrophages},
author = {Koike, Eiko and Kobayashi, Takahiro},
abstractNote = {We hypothesized that diesel exhaust particles (DEP) induce the activation of antigen-presenting cells (APC) in lung. The present study was designed to clarify the following about DEP: (1) whether it affects the expression of Ia and B7 molecules in alveolar macrophages (AM) as a mature cell or in peripheral blood monocytes (PBM) as an immature cell (2) if it affects the antigen-presenting (AP) activity of PBM (3) what component of DEP is responsible for the effects, and (4) whether the effect of DEP is related to oxidative stress. DEP was extracted with methylene chloride. Cells were exposed to whole DEP, organic extract, or residual particles for 24 h. Cell-surface molecules were measured by flow cytometry. AP activity was assessed by antigen-specific T cell proliferation. Whole DEP or organic extract significantly increased the expression of Ia and B7 molecules on PBM but not on AM. No significant effect of residual particles was observed. A low concentration of organic extract also increased the AP activity of PBM. When the induction of an antioxidative enzyme was assessed, heme oxygenase-1 protein was found to be significantly increased by exposure to whole DEP, and the organic extract was more effective than the residual particles. Furthermore, the organic extract-induced expression of Ia antigen on PBM was reduced by the addition of an antioxidative agent. These results suggest that DEP may act on immature APC and enhance their AP activity and that the action contributing to oxidative stress may be mediated by organic compounds of DEP.},
doi = {10.1016/j.taap.2005.04.017},
journal = {Toxicology and Applied Pharmacology},
number = 3,
volume = 209,
place = {United States},
year = {Thu Dec 15 00:00:00 EST 2005},
month = {Thu Dec 15 00:00:00 EST 2005}
}
  • The use of diesel-powered equipment in underground mines has raised questions regarding possible synergistic effects of coal dust and diesel emissions. Therefore, the effects of chronic exposure of rats to coal dust and/or diesel exhaust on various properties of alveolar macrophages were investigated. Inhalation exposure of rats was 7 hr/day, 5 days/week for 2 years. Exposure groups were: filtered air controls, 2 mg/m/sup 3/ coal dust, 2 mg/m/sup 3/ diesel particulates, and 1 mg/m/sup 3/ coal dust plus 1 mg/m/sup 3/ diesel exhaust. Exposure to coal dust and/or diesel exhaust had little effect on oxygen consumption, membrane integrity, lysosomal enzymemore » activity, or protein content of alveolar macrophages. However, exposure to coal dust increased macrophage yield, enhanced chemiluminescence, and increased the activity of the cell membrane (i.e., increased cellular spreading and surface ruffling). In contrast, diesel emissions depressed chemiluminescence and decreased the ruffling of the cell membrane. Therefore, the data suggest that exposure to coal dust and/or diesel exhaust does not affect the viability of alveolar macrophages. However, coal dust may activate alveolar macrophages while diesel emissions may depress the phagocytic activity of these cells. The combination of exposures to coal dust and diesel exhaust results in a phagocytic activity which is an average of the effects of separate exposures.« less
  • Radiolabeled diesel exhaust particles or dichloromethane extracts of these particles were intratracheally instilled (10 mg) into Fischer-344 rats and the clearance of 14C radioactivity was measured. Approximately 88% of the 14C radioactivity associated with the particles was soluble in dichloromethane. The clearance of 14C radioactivity from lungs occurred in two phases. The initial, more rapid phase of lung clearance of both particle-associated 14C radioactivity (Particle 14C) and extract-associated 14C radioactivity (Extract 14C) was very similar (t 1/2 approximately equal to 3 hr). However, the second phase of lung clearance of the remaining Particle 14C was much slower (t 1/2 approximatelymore » equal to 25 days) than the second phase of lung clearance of the Extract 14C (t 1/2 approximately equal to 2.9 days). Tracheal clearance rates of 14C radioactivity from both instillation studies were both rapid and similar (t 1/2 approximately equal to 10-12 hr). These results indicate that diesel engine exhaust particles reduce the lung clearance rate of the organic compounds associated with these particles. These studies also point to the possibility that the rate limiting step in the lung clearance of organic compounds associated with inhaled diesel exhaust particles may be the rate at which they dissociate from these particles in vivo. This is because the long-term clearance rate of the particle-associated organic compounds was shown here to be much slower than that of the same organic compounds in a particle-free form but not as slow as the lung clearance rate reported for diesel exhaust core particles (T.L. Chan, P.S. Lee, W.E. Hering, J. Appl. Toxicol. 1, 77-82 (1981)).« less
  • The accessory cell function of purified alveolar macrophages (MP) was compared with that of peripheral blood monocytes (MN) by assaying the ability of each to support the OKT3 antibody induced proliferation of purified T cells (TC). TC (1 x 10/sup 5/) co-cultured with 0.3 to 8 x 10/sup 4/ autologous MP or MN were exposed to 5 ng/ml of OKT3 antibody for 64 hrs, with /sup 3/H-thymidine present for the last 16 hrs of culture. TC, MN or MP cultured alone with OKT3 antibody resulted in /sup 3/HT incorporation of < 900 cpms. TC + 10% MP cultured with OKT3more » antibody gave 3600 to 41,990 cpm which was 2 to 4 fold better than the level seen with cultures of TC + 10% MN + OKT3. The addition of increasing numbers of MN to TC + OKT3 cultures could increase the level of proliferation to that found with MP + TC + OKT3. TC + 10% MP + OKT3 cultures contained 1.5 to 3 fold more IL2 receptor positive cells and demonstrated greater IL2 production than did cultures of TC + 10% MN + OKT3. Therefore, on a cell to cell comparison, MP are much more active than MN in accessory cell function in supporting TC proliferation, induction of IL2 receptors and IL2 production.« less
  • Pulmonary epithelial lining fluid (ELF) is the first substance to make contact with inhaled particulate matter (PM) and interacts chemically with PM components. The objective of this study was to determine the role of ELF in oxidative stress, DNA damage and the production of proinflammatory cytokines following physicochemical exposure to PM. Ultrafine carbon black (ufCB, 15 nm; a model carbonaceous core), ferrous sulphate (FeSO{sub 4}; a model transition metal) and a diesel exhaust particle (DEP) extract (a model organic compound) were used to examine the acellular oxidative potential of synthetic ELF and non-ELF systems. We compared the effects of exposuremore » to ufCB, FeSO{sub 4} and DEP extract on human alveolar epithelial Type II (A549) cells to determine the levels of oxidative stress, DNA single-strand breaks and interleukin-8 (IL-8) production in ELF and non-ELF systems. The effects of ufCB and FeSO{sub 4} on the acellular oxidative potential, cellular oxidative stress and DNA single-strand breakage were mitigated significantly by the addition of ELF, whereas there was no decrease following treatment with the DEP extract. There was no significant effect on IL-8 production following exposure to samples that were suspended in ELF/non-ELF systems. The results of the present study indicate that ELF plays an important role in the initial defence against PM in the pulmonary environment. Experimental components, such as ufCB and FeSO{sub 4}, induced the production of oxidative stress and led to DNA single-strand breaks, which were moderately prevented by the addition of ELF. These findings suggest that ELF plays a protective role against PM-driven oxidative stress and DNA damage. -- Highlights: ► To determine the role of ELF in ROS, DNA damage and IL-8 after exposure to PM. ► ufCB, FeSO{sub 4} and DEP extract were used to examine the protective effects of ELF. ► PM-driven oxidative stress and DNA single-strand breakage were mitigated by ELF. ► The findings suggest that ELF has a protective role against PM. ► The synthetic ELF system could reduce the use of animals in PM-driven ROS testing.« less