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Effects of prenatal diesel exhaust inhalation on pulmonary inflammation and development of specific immune responses
Citation:
SHARKHUU, T., D. L. DOERFLER, Q. T. KRANTZ, R. W. LUEBKE, W. P. LINAK, AND M. I. GILMOUR. Effects of prenatal diesel exhaust inhalation on pulmonary inflammation and development of specific immune responses. TOXICOLOGY LETTERS. Elsevier Science Ltd, New York, NY, 196(1):12-20, (2010).
Impact/Purpose:
In utero exposure to environmental agents during fetal development can dramatically influence the magnitude and type of immune responses after birth (Wang et al., 2008), and in later life (Hamada et aI., 2007). Reported effects include immunosuppression (Burns-Nass et al., 2008; Dietert and Zelikoff 2008) as well as enhanced sensitization to allergens (Fedulov et al, 2008) following istillation ofdiesel and other particles. Because there is emerging evidence to suggest that traffic-related pollutants increase the incidence ofallergic asthma, this study was designed to investigate whether an analogous phenomenon occurred in murine offspring exposed in utero to different levels of freshly generated and diluted diesel exhaust.
Description:
There is increasing evidence that exposure to air pollutants during pregnancy can result in a number of deleterious effects including low birth weight and the incidence of allergic asthma. To investigate the in utero effects of DE exposure, timed pregnant BALB/c mice were exposed to 0, 0.8 or 3.1mg/m(3) of DE during gestation days (GD) 9 to GD18. The number of successful pregnancies was 15/20 in the air controls and 10/20 in each of the diesel exposures. Immune function in the six week old offspring as determined by development of delayed type hypersensitivity (DTH) reactions to bovine serum albumin (BSA), antibody titers to injected sheep red blood cells (SRBC), splenic T cells expressing CD45(+)CD3(+)CD8(+) and CD3(+)CD25(+), and mRNA expression of TNF-alpha, TLR2, SP-A, TGF-beta and Foxp3 in the lung were not affected by pre-natal DE exposure. On the other hand, lung TLR4 mRNA expression, the number of neutrophils in the bronchoalveolar lavage fluid (BALF) and splenic T cells expressing CD45(+)CD3(+)CD4(+) and CD4(+)CD25(+) were differentially affected depending on the DE concentration and gender. When additional groups of mice were sensitized and challenged via the respiratory tract with ovalbumin antigen to induce allergic airway inflammation, the female mice had higher protein higher protein levels in the BALF compared to males and this was reduced by reduced by prenatal exposure to either concentration of DE. No other changes in allergen-induced immunity, lung function or severity of inflammation were noted. Collectively, the results show that in utero exposure to DE altered some baseline inflammatory indices in the lung in a gender specific manner, but had no effect on development of specific immune responses to experimental antigens, or the severity of allergic lung inflammation. Copyright © 2010. Published by Elsevier Ireland Ltd.
