UVM Theses and Dissertations
Format:
Print
Author:
Foster, Samantha Ruth
Dept./Program:
Cell and Molecular Biology Program
Year:
2009
Degree:
M.S.
Abstract:
Nitrogen dioxide (NO₂) is a component of air pollution associated with poor respiratory health and exacerbation of asthma, particularly in children. Furthermore, associations have been made between NO₂ and an increased likelihood of inhalational allergies. In mice, NO₂ worsens the pathophysiology of pre-existing allergic asthma and can also act as an adjuvant, allowing for allergic sensitization to the innocuous antigen, ovalbumin (ova). As dendritic cells (DCs) are thought to be critical for naive T cell activation, we hypothesized that NO₂ functions as an adjuvant by inducing the recruitment or activation of DCs. We performed flow cytometric analyses of DC populations within the lung and the lung-draining lymph node, the mediastinal lymph node (MLN). Two hours following exposure to 15ppm NO₂ and ova, CD11c pulmonary DCs showed a significant increase in MHCII expression and upregulated QX40L, indicating improved ability to present antigen and provide co-stimulation to activate naive T cells.
By 48 hours post exposure, CD11cMHCn⁺ DCs within the MLN also showed signs of maturation, including substantial increases in CD80, CD86, and OX40L expression. These dendritic cells were 37.5% CD11b⁺ in NO₂ treated mice versus 23.7% CD11b⁺ in air treated mice, indicating that CD 11c⁺CD11b⁺ cells may be recruited to the lung and travel to the MLN following NO₂ exposure, potentially playing an important role in naIve T cell activation during NO₂-induced allergic sensitization. Furthermore, CD11c+ pulmonary cells exposed to NO₂ increased antigen capture of ova-Alexa 647 and produced significant amounts of IL-1a, 1L-1B, and 1L-6 compared to air controls, indicating an improved ability to initiate and shape a Th2 biased immune response. Lastly, when CD11c⁺ cells were depleted during sensitization, mice exhibited less inflammation within the lung following allergen challenge, implying that CD11c⁺ dendritic cells play an important role during NO₂-induced allergic sensitization.
By 48 hours post exposure, CD11cMHCn⁺ DCs within the MLN also showed signs of maturation, including substantial increases in CD80, CD86, and OX40L expression. These dendritic cells were 37.5% CD11b⁺ in NO₂ treated mice versus 23.7% CD11b⁺ in air treated mice, indicating that CD 11c⁺CD11b⁺ cells may be recruited to the lung and travel to the MLN following NO₂ exposure, potentially playing an important role in naIve T cell activation during NO₂-induced allergic sensitization. Furthermore, CD11c+ pulmonary cells exposed to NO₂ increased antigen capture of ova-Alexa 647 and produced significant amounts of IL-1a, 1L-1B, and 1L-6 compared to air controls, indicating an improved ability to initiate and shape a Th2 biased immune response. Lastly, when CD11c⁺ cells were depleted during sensitization, mice exhibited less inflammation within the lung following allergen challenge, implying that CD11c⁺ dendritic cells play an important role during NO₂-induced allergic sensitization.