The Laboratory-Based Respiratory Mechanistic Research Project Mechanistic Research Project: In Utero Sensitization to Allergens and the Role of Environmental Pollutants. Recent evidence suggests that antigen sensitization, defined as antigen-induced cord blood mononuclear cell (CPMC) proliferation assays, occurs prenatally. For example, our work demonstrates that antigen-induced CBMC proliferation occurs following in vitro stimulation with multiple inhaled indoor allergens prevalent in inner-cities, including cockroach and mouse. Other experimental research has indicated that diesel exhaust particulates (DEP), and particularly the polycyclic aromatic hydrocarbon (PAH) component of DEP, can augment antigen-specific sensitization and IgE-mediated processes. The occurrence of antigen-specific immune responses in utero may have important implications for the subsequent onset of respiratory disease, particularly in light of the high prevalence of both environmental indoor allergens and DEP in northern Manhattan and elsewhere, and their apparent role in asthma. Yet the effect of prenatal sensitization on subsequent airway hyperreactivity and antigen-induced inflammation characteristic of asthma is not understood. In addition, the importance of environmental pollutants (egs DEP, endotoxin) to the onset of prenatal antigen-specific sensitization also has not been elucidated. The project will test the hypotheses that in utero sensitization increases the risk for subsequent airway hyperreactivity and antigen-induced inflammation, and that environmental exposure to DEP promotes antigen-specific sensitization in utero, whereas exposure to endotoxin is protective. The goal is to use mouse models to determine the importance of in utero sensitization to subsequent airway hyperreactivity and inflammation, and to determine whether the mechanism of in utero sensitization involves the interaction of multiple urban environmental exposures. Ultimately, these studies could lead to a better understanding of asthma pathogenesis, and ultimately better strategies for asthma prevention. Specifically, the aims are to:
Aim 1. Determine whether in utero sensitization increases the risk for subsequent airway hyperreactivity and antigen-induced inflammation.
Aim 2. Determine whether DEP, endemic to the northern Manhattan environment, promote antigen-specific prenatal sensitization, and whether this occurs by upregulating Th2-mediated allergic responses. We will also determine whether PAH, measured by PAH-adducts in lung tissue, mediates this response.
Aim 3. Determine whether endotoxin protects from the development of antigen-specific prenatal sensitization, and whether this occurs by upregulating Th1-mediated immune processes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Program Projects (P01)
Project #
5P01ES009600-08
Application #
7176788
Study Section
Special Emphasis Panel (ZES1)
Project Start
Project End
Budget Start
2005-11-01
Budget End
2006-10-31
Support Year
8
Fiscal Year
2006
Total Cost
$58,355
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
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Bansal, Ravi; Peterson, Bradley S (2018) Cluster-level statistical inference in fMRI datasets: The unexpected behavior of random fields in high dimensions. Magn Reson Imaging 49:101-115
Lovinsky-Desir, Stephanie; Lawrence, Jennifer; Jung, Kyung Hwa et al. (2018) Assessment of exposure to air pollution in children: Determining whether wearing a personal monitor affects physical activity. Environ Res 166:340-343
Perera, Frederica P; Wheelock, Kylie; Wang, Ya et al. (2018) Combined effects of prenatal exposure to polycyclic aromatic hydrocarbons and material hardship on child ADHD behavior problems. Environ Res 160:506-513
Jung, Kyung Hwa; Lovinsky-Desir, Stephanie; Yan, Beizhan et al. (2017) Effect of personal exposure to black carbon on changes in allergic asthma gene methylation measured 5 days later in urban children: importance of allergic sensitization. Clin Epigenetics 9:61
Lovinsky-Desir, Stephanie; Jung, Kyung Hwa; Jezioro, Jacqueline R et al. (2017) Physical activity, black carbon exposure, and DNA methylation in the FOXP3 promoter. Clin Epigenetics 9:65
Jung, Kyung Hwa; Torrone, David; Lovinsky-Desir, Stephanie et al. (2017) Short-term exposure to PM2.5 and vanadium and changes in asthma gene DNA methylation and lung function decrements among urban children. Respir Res 18:63
Harley, Kim G; Engel, Stephanie M; Vedar, Michelle G et al. (2016) Prenatal Exposure to Organophosphorous Pesticides and Fetal Growth: Pooled Results from Four Longitudinal Birth Cohort Studies. Environ Health Perspect 124:1084-92
Lovinsky-Desir, Stephanie; Jung, Kyung Hwa; Rundle, Andrew G et al. (2016) Physical activity, black carbon exposure and airway inflammation in an urban adolescent cohort. Environ Res 151:756-762
Lovinsky-Desir, Stephanie; Miller, Rachel L; Bautista, Joshua et al. (2016) Differences in Ambient Polycyclic Aromatic Hydrocarbon Concentrations between Streets and Alleys in New York City: Open Space vs. Semi-Closed Space. Int J Environ Res Public Health 13:

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