Diesel exhaust particles suppress macrophage function and slow the pulmonary clearance of Listeria monocytogenes in rats.

Abstract

In this study, we tested the hypothesis that exposure to diesel exhaust particles (DEP) may increase susceptibility of the host to pulmonary infection. Male Sprague-Dawley rats received a single dose of DEP (5 mg/kg), carbon black (CB, 5 mg/kg), or saline intratracheally. Three days later, the rats were inoculated intratracheally with approximately 5,000 Listeria monocytogenes and sacrificed at 3, 5, and 7 days postinfection, and we determined the number of viable Listeria in the left lobe of lungs. The remaining lungs underwent bronchoalveolar lavage (BAL) and the retrieved BAL cells were identified and counted. Luminol-dependent chemiluminescence, a measure of reactive oxygen species (ROS) formation, generated by BAL cells was monitored and the levels of nitric oxide and tumor necrosis factor (TNF)-[alpha] produced by macrophages in culture were determined. At 7 days postinfection, we excised the lung-draining lymph nodes and phenotyped the lymphocyte subpopulations. Exposure of rats to DEP, but not to CB, decreased the clearance of Listeria from the lungs. Listeria-induced generation of luminol-dependent chemiluminescence by pulmonary phagocytes decreased by exposure to DEP but not CB. Similarly, Listeria-induced production of NO by alveolar macrophages was negated at 3, 5, and 7 days after inoculation in DEP-exposed rats. In contrast, CB exposure had no effect on Listeria-induced NO production at 3 days after infection and had a substantially smaller effect than DEP at later days. Exposure to DEP or CB resulted in enlarged lung-draining lymph nodes and increased the number and percentage of CD4(+) and CD8(+) T cells. These results showed that exposure to DEP decreased the ability of macrophages to produce antimicrobial oxidants in response to Listeria, which may play a role in the increased susceptibility of rats to pulmonary infection. This DEP-induced suppression is caused partially by chemicals adsorbed onto the carbon core of DEP, because impaired macrophage function and decreased Listeria clearance were not observed following exposure to CB.

Cytotoxicity and Characterization of Particles Collected From an Indium–Tin Oxide Production Facility

“…This may explain the caspase activation that was seen at 24 h postexposure in RAW cells ( Figure 7A). Macrophage dysfunction and toxicity from particle overload were observed in several previous studies, where cells preloaded with various particles can not perform their phagocytic duty (Lundborg et al, 2006;Zhou and Kobzik, 2007;Yang et al, 2001;Oberdorster, 1995) and succumb to toxicity from the engulfed particles (Allison et al, 1966;Hiura et al, 1999;Li et al, 2002).…”

Sequential Exposure to Carbon Nanotubes and Bacteria Enhances Pulmonary Inflammation and Infectivity

“…On the other hand, Saxena and coworkers showed that exposure of mouse AMs to diesel exhaust particles attenuated IFN-ginduced production of NO (36). In addition, pulmonary exposure of rats to diesel exhaust particles depressed NO production by AMs in response to pulmonary LM infection and depressed bacterial clearance (37). Similarly, pulmonary exposure to ROFA enhanced zymosan-stimulated chemiluminescence in rat AMs but reduced NO release and bacterial clearance in response to the same stimulus (38).…”

Nickel Alterations of TLR2-Dependent Chemokine Profiles in Lung Fibroblasts Are Mediated by COX-2

“…There are reports, however, of increased numbers of hospitalizations for respiratory disorders including infections on days of increased levels of PM (2). In support of these epidemiologic findings, several rodent models have shown PM exposure can increase susceptibility to infectious bacteria such as Listeria monocytogenes and Streptococcus pneumoniae (3,4).…”