Effect of diesel exhaust particulate (DEP) on bacillus Calmette-Guerin (BCG) lung infection in mice.
Lewis-DM; Saxena-QB; Weissman-DN; Simpson-JP; Bledsoe-TA; Saxena-RK
Toxicologist 2003 Mar; 72(S-1):375
The effect of exposure to diesel exhaust particulate (DEP) on Bacillus Calmette-Guerin (BCG) lung infection in mice was studied. C57Bl6 female mice were infected with BCG (2.5x10^4 bacteria/mouse) by tracheal aspiration with or without co-administration of DEP (100 mcg/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 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 and expression levels were similar in mice exposed to BCG or BCG+DEP. Recovery of IFN gamma secreting T cells was significantly higher (p<0.05) from lungs of BCG and BCG + DEP infected mice as compared to control or DEP only exposed mice, but BCG and BCG+DEP groups of mice were not significantly different. 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, in vitro studies demonstrated DEP treatment inhibited IFN gamma induced nitric oxide secretion by mouse alveolar macrophages. Thus, DEP exposure did not alter the IFN gamma response to BCG infection, but reduced a key microbiocidal response of macrophages to IFN gamma. Reduced responsiveness of DEP exposed macrophages to IFN gamma may contribute to a less efficient clearance of BCG from the lungs of BCG infected mice.
Diesel-exhausts; Particulate-dust; Particulates; Lung-disorders; Laboratory-animals; Animal-studies; Animals; Lymphocytes; Pulmonary-disorders; Pulmonary-system; In-vitro-studies; Combustion-products; Combustion-gases
The Toxicologist. Society of Toxicology 42nd Annual Meeting and ToxExpo, Cutting-Edge Science, Networking, New Perspectives, March 9-13, 2003, Salt Lake City, Utah