skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Soluble metals in residual oil fly ash alter innate and adaptive pulmonary immune responses to bacterial infection in rats

Abstract

The soluble metals of the pollutant, residual oil fly ash (ROFA), have been shown to alter pulmonary bacterial clearance in rats. The goal of this study was to determine the potential effects on both the innate and adaptive lung immune responses after bacterial infection in rats pre-exposed to the soluble metals in ROFA. Sprague-Dawley rats were intratracheally dosed (i.t.) at day 0 with ROFA (R-Total) (1.0 mg/100 g body weight), the soluble fraction of ROFA (R-Soluble), the soluble sample subject to a chelator (R-Chelex), or phosphate-buffered saline (Saline). On day 3, rats were administered an i.t. dose of 5 x 10{sup 4} Listeria monocytogenes. On days 6, 8, and 10, bacterial pulmonary clearance was monitored and bronchoalveolar lavage (BAL) was performed on days 3 (pre-infection), 6, 8, and 10. A concentrated first fraction of lavage fluid was retained for analysis of lactate dehydrogenase and albumin to assess lung injury. BAL cell number, phenotype, and production of reactive oxygen (ROS) and nitrogen species (RNS) were assessed, and a variety of cytokines were measured in the BAL fluid. Rats pre-treated with R-Soluble showed elevated lung injury/cytotoxicity and increased cellular influx into the lungs. R-Soluble-treatment also altered ROS, RNS, and cytokine levels, andmore » caused a degree of macrophage and T cell inhibition. These effects of R-Soluble result in increased pulmonary bacterial burden after infection. The results suggest that soluble metals in ROFA increase lung injury and inflammation, and alter both innate and adaptive pulmonary immune responses.« less

Authors:
 [1];  [2];  [2];  [3];  [2];  [3]
  1. Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States) and West Virginia University, Morgantown, WV 26505 (United States). E-mail: jur6@cdc.gov
  2. Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States)
  3. (United States)
Publication Date:
OSTI Identifier:
20976959
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 221; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2007.03.022; PII: S0041-008X(07)00142-1; Copyright (c) 2007 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; ALBUMINS; FLY ASH; INFLAMMATION; INJURIES; LACTATE DEHYDROGENASE; LAVAGE; LUNGS; LYMPHOKINES; MACROPHAGES; METALS; PETROLEUM RESIDUES; PHENOTYPE; PHOSPHATES; POLLUTANTS; RATS; TOXICITY

Citation Formats

Roberts, Jenny R., Young, Shih-Houng, Castranova, Vincent, West Virginia University, Morgantown, WV 26505, Antonini, James M., and West Virginia University, Morgantown, WV 26505. Soluble metals in residual oil fly ash alter innate and adaptive pulmonary immune responses to bacterial infection in rats. United States: N. p., 2007. Web. doi:10.1016/j.taap.2007.03.022.
Roberts, Jenny R., Young, Shih-Houng, Castranova, Vincent, West Virginia University, Morgantown, WV 26505, Antonini, James M., & West Virginia University, Morgantown, WV 26505. Soluble metals in residual oil fly ash alter innate and adaptive pulmonary immune responses to bacterial infection in rats. United States. doi:10.1016/j.taap.2007.03.022.
Roberts, Jenny R., Young, Shih-Houng, Castranova, Vincent, West Virginia University, Morgantown, WV 26505, Antonini, James M., and West Virginia University, Morgantown, WV 26505. 2007. "Soluble metals in residual oil fly ash alter innate and adaptive pulmonary immune responses to bacterial infection in rats". United States. doi:10.1016/j.taap.2007.03.022.
@article{osti_20976959,
title = {Soluble metals in residual oil fly ash alter innate and adaptive pulmonary immune responses to bacterial infection in rats},
author = {Roberts, Jenny R. and Young, Shih-Houng and Castranova, Vincent and West Virginia University, Morgantown, WV 26505 and Antonini, James M. and West Virginia University, Morgantown, WV 26505},
abstractNote = {The soluble metals of the pollutant, residual oil fly ash (ROFA), have been shown to alter pulmonary bacterial clearance in rats. The goal of this study was to determine the potential effects on both the innate and adaptive lung immune responses after bacterial infection in rats pre-exposed to the soluble metals in ROFA. Sprague-Dawley rats were intratracheally dosed (i.t.) at day 0 with ROFA (R-Total) (1.0 mg/100 g body weight), the soluble fraction of ROFA (R-Soluble), the soluble sample subject to a chelator (R-Chelex), or phosphate-buffered saline (Saline). On day 3, rats were administered an i.t. dose of 5 x 10{sup 4} Listeria monocytogenes. On days 6, 8, and 10, bacterial pulmonary clearance was monitored and bronchoalveolar lavage (BAL) was performed on days 3 (pre-infection), 6, 8, and 10. A concentrated first fraction of lavage fluid was retained for analysis of lactate dehydrogenase and albumin to assess lung injury. BAL cell number, phenotype, and production of reactive oxygen (ROS) and nitrogen species (RNS) were assessed, and a variety of cytokines were measured in the BAL fluid. Rats pre-treated with R-Soluble showed elevated lung injury/cytotoxicity and increased cellular influx into the lungs. R-Soluble-treatment also altered ROS, RNS, and cytokine levels, and caused a degree of macrophage and T cell inhibition. These effects of R-Soluble result in increased pulmonary bacterial burden after infection. The results suggest that soluble metals in ROFA increase lung injury and inflammation, and alter both innate and adaptive pulmonary immune responses.},
doi = {10.1016/j.taap.2007.03.022},
journal = {Toxicology and Applied Pharmacology},
number = 3,
volume = 221,
place = {United States},
year = 2007,
month = 6
}
  • Intranasal application of vesicular stomatitis virus (VSV) causes acute infection of the central nervous system (CNS). However, VSV encephalitis is not invariably fatal, suggesting that the CNS may contain a professional antigen-presenting cell (APC) capable of inducing or propagating a protective antiviral immune response. To examine this possibility, we first characterized the cellular elements that infiltrate the brain as well as the activation status of resident microglia in the brains of normal and transgenic mice acutely ablated of peripheral dendritic cells (DCs) in vivo. VSV encephalitis was characterized by a pronounced infiltrate of myeloid cells (CD45{sup high}CD11b{sup +}) and CD8{supmore » +} T cells containing a subset that was specific for the immunodominant VSV nuclear protein epitope. This T cell response correlated temporally with a rapid and sustained upregulation of MHC class I expression on microglia, whereas class II expression was markedly delayed. Ablation of peripheral DCs profoundly inhibited the inflammatory response as well as infiltration of virus-specific CD8{sup +} T cells. Unexpectedly, the VSV-induced interferon-gamma (IFN-gamma) response in the CNS remained intact in DC-deficient mice. Thus, both the inflammatory and certain components of the adaptive primary antiviral immune response in the CNS are dependent on peripheral DCs in vivo.« less
  • A rat model of chronic pulmonary infection (CPI) initiated by Pseudomonas aeruginosa embedded in agar beads was used to test the effect of ozone on lysosomal enzyme levels in alveolar macrophages (AM). CPI was induced by intratracheal instillation of a 0.1-ml suspension of infected beads into the left lung. Ten days after infection half the rats were exposed to atmospheres of air and half to 0.64 ppm ozone for 4 weeks. Enzyme levels were measured using a scanning cytospectrophotometer linked to a PDP/11 computer. Measurement of lysozyme in individual rat AM in situ showed a significant decrease in cell sizemore » and enzyme content in ozone-exposed uninfected animals. Cell size and enzyme content of ozone-exposed animals with CPI were further reduced, suggesting a synergistic effect between ozone exposure and chronic infection.« less
  • Rats were chronically infected with Pseudomonas aeruginosa by entrapping viable bacteria in agar beads and intratracheally inoculating the beads into the left lung. The infection was allowed to stabilize over a 10-d period and the animals were then placed in environmental chambers and exposed to either filtered air or 0.64 ppm ozone (23 h/d) for 14 or 28 d. Rats exposed to ozone had reduced body weight and increased lung sizes and lung weights compared with animals breathing filtered air. Rats inoculated with beads containing live P. aeruginosa had increased lung weights when compared with rats inoculated with beads containingmore » heat-killed P. aeruginosa or controls. Quantitation of total viable bacteria in rats exposed to ozone or to filtered air revealed no significant differences in bacterial numbers. Thus, in this model, chronic exposure to ozone produces increases in lung volume and weight but does not enhance a smoldering Pseudomonas infection. 28 references, 1 figure, 2 tables.« less
  • Epidemiology suggests that inhalation of welding fumes increases the susceptibility to lung infection. The effects of chemically distinct welding fumes on lung defense responses after bacterial infection were compared. Fume was collected during gas metal arc (GMA) or flux-covered manual metal arc (MMA) welding using two consumable electrodes: stainless steel (SS) or mild steel (MS). The fumes were separated into water-soluble and -insoluble fractions. The GMA-SS and GMA-MS fumes were found to be relatively insoluble, whereas the MMA-SS was highly water soluble, with the soluble fraction comprised of 87% Cr and 11% Mn. On day 0, male Sprague-Dawley rats weremore » intratracheally instilled with saline (vehicle control) or the different welding fumes (0.1 or 2 mg/rat). At day 3, the rats were intratracheally inoculated with 5 x 10{sup 3} Listeria monocytogenes. On days 6, 8, and 10, left lungs were removed, homogenized, cultured overnight, and colony-forming units were counted to assess pulmonary bacterial clearance. Bronchoalveolar lavage (BAL) was performed on right lungs to recover phagocytes and BAL fluid to measure the production of nitric oxide (NO) and immunomodulatory cytokines, including tumor necrosis factor-{alpha} (TNF-{alpha}), interleukin (IL)-2, IL-6, and IL-10. In contrast to the GMA-SS, GMA-MS, and saline groups, pretreatment with the highly water soluble MMA-SS fume caused significant body weight loss, extensive lung damage, and a dramatic reduction in pulmonary clearance of L. monocytogenes after infection. NO concentrations in BAL fluid and lung immunostaining of inducible NO synthase were dramatically increased in rats pretreated with MMA-SS before and after infection. MMA-SS treatment caused a significant decrease in IL-2 and significant increases in TNF-{alpha}, IL-6, and IL-10 after infection. In conclusion, pretreatment with MMA-SS increased production of NO and proinflammatory cytokines (TNF-{alpha} and IL-6) after infection, which are likely responsible for the elevation in lung inflammation and injury. In addition, MMA-SS treatment reduced IL-2 (involved in T cell proliferation) and enhanced IL-10 (involved in inhibiting macrophage function) after bacterial infection, which might result in a possible suppression in immune response and an increase in susceptibility to infection.« less