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ToxSci Advance Access published online on April 15, 2003

Toxicological Sciences, doi:10.1093/toxsci/kfg048
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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Received November 25, 2002; accepted January 23, 2003
© 2003 Society of Toxicology

Immunotoxicology

Effect of Diesel Exhaust Particulate (DEP) on Bacillus Calmette-Guerin (BCG) Lung Infection in Mice and the Attendant Changes in Lung Interstitial Lymphoid Subpopulations and IFN{gamma} response

Rajiv K. Saxena 1, Queen B. Saxena 2, David N. Weissman 3, Janet P. Simpson 3, Toni A. Bledsoe 3, Daniel M. Lewis 3*

1 School of Life Sciences, Jawaharlal Nehru University, New Delhi; ASB, HELD, NIOSH, Center of Disease Control and Prevention, Morgantown, WV
2 Indian Council of Medical Research, New Delhi; ASB, HELD, NIOSH, Center of Disease Control and Prevention, Morgantown, WV
3 ASB, HELD, NIOSH, Center of Disease Control and Prevention, Morgantown, WV

* To whom correspondence should be addressed. E-mail: dlewis{at}cdc.gov.


   Abstract

The effect of exposure to diesel exhaust particulate (DEP) on Bacillus Calmette-Guerin (BCG) lung infection in mice was studied. C57B1/6J female mice were infected with BCG (2.5x104 bacteria/mouse) by intrapulmonary instillation with or without co-administration of DEP (100µg/mouse). Five weeks later, mice exposed to DEP+BCG had about four-fold higher BCG load in lungs than mice exposed only to BCG (p<0.05). DEP treatment alone had no effect on the total number of lung lymphocytes or numbers of T, B or NK cells recovered from lungs. In contrast, BCG infection significantly increased (p<0.05) recovery of all types of lymphocytes from lungs. Co-exposure to DEP+BCG further increased the recovery of lymphocytes from lungs of BCG infected mice. The pulmonary lymphocyte subpopulation expressing the greatest levels of mRNA for IFN{gamma} after BCG infection was CD4+ T cells. Expression levels were similar in mice exposed to BCG or BCG+DEP and were elevated as compared to non-infected mice and mice treated with DEP alone. Recovery of IFN{gamma} secreting lymphocytes and IFN{gamma} secreting T cells was significantly higher (p<0.05) from lungs of BCG infected mice as compared to control or DEP exposed mice. BCG and BCG+DEP groups of mice did not differ significantly in the numbers of IFN{gamma} secreting lymphocytes in lungs. Taken together, these results indicated that co-exposure to DEP+BCG did not significantly affect the level of IFN{gamma} response of mice to BCG infection. However, DEP treatment was found to inhibit IFN{gamma} induced nitric oxide production by mouse alveolar macrophages in vitro. Our results indicate that DEP exposure did not alter the IFN{gamma} response to BCG infection, but reduced responsiveness of alveolar macrophages to IFN{gamma}. Reduced sensitivity of DEP exposed alveolar macrophages to IFN{gamma} may contribute to a greater load of BCG in the lungs of BCG infected mice given DEP.

Diesel exhaust, BCG, Interferon, T cells, NK cells, macrophages, nitric oxide, lung, infection .


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