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Hui-Min Yang,¹ James M. Antonini,¹ Mark W. Barger,¹ Leon Butterworth,¹ Jenny R. Roberts,¹ Joseph K.H. Ma,² Vince Castranova,¹ and Jane Y.C. Ma¹

¹Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA; ²School of Pharmacy, West Virginia University, Morgantown, West Virginia, USA

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 ~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) - 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. Key words: alveolar macrophages, diesel exhaust particles, Listeria monocytogenes, lung clearance, lung-draining lymph nodes, reactive oxidative species, tumor necrosis factor-, T cells. Environ Health Perspect 109:515-521 (2001) . [Online 11 May 2001]

http://ehpnet1.niehs.nih.gov/docs/2001/109p515-521yang/ abstract.html

Address correspondence to H-M Yang, Mail Stop 2015, PPRB/HELD, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505 USA. Telephone: (304) 285-6172. Fax: (304) 285-5938. E-mail: hay7@cdc.gov

This work was presented in part at the 38th annual meeting of the Society of Toxicology, New Orleans, Louisiana, 14-19 March 1999.

Received 19 August 2000 ; accepted 30 November 2000.