Effects of prenatal diesel exhaust inhalation on pulmonary inflammation and development of specific immune responses.
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 3.1 mg/m(3) of DE during gestation days (GD) 9 to GD 18. 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 6-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 prenatal 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 to induce allergic airway inflammation, female mice had higher protein levels in the BALF compared to males and this was 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.
Sharkhuu
Tuya
T
Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, NHEERL, US Environmental Protection Agency (EPA), Research Triangle Park, North Carolina 27711, United States.
Doerfler
Donald L
DL
Krantz
Q Todd
QT
Luebke
Robert W
RW
Linak
William P
WP
Gilmour
M Ian
MI
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001273:Atmosphere Exposure Chambers; D016207:Cytokines / Q000378:metabolism; D005260:Female; D000922:Immunotoxins / Q000378:metabolism; D019570:Inhalation Exposure; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology; D011247:Pregnancy; D012130:Respiratory Hypersensitivity / Q000209:etiology* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001335:Vehicle Emissions / Q000633:toxicity*
D000393:Air Pollutants; D015703:Antigens, CD; D016207:Cytokines; D000922:Immunotoxins; D001335:Vehicle Emissions