All ETDs from UAB

Advisory Committee Chair

Edward M Postlethwait

Advisory Committee Members

Michelle V Fanucchi

Shannon M Bailey

David D Chaplin

Lisa M Schwiebert

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) School of Public Health


Environmental ozone exposure remains a major public health concern with over one-third of the United States population experiencing unhealthful levels. Epidemiological studies indicate exposure increases morbidity in those with pre-existing disease such as asthma, though the biological mechanisms underlying this phenomenon remain elusive. CD11c+ cells within the respiratory tract include dendritic cells (DCs), which are the most efficient antigen presenters and play major roles controlling immune responses. In addition, DCs are thought necessary for asthma pathogenesis and exacerbation. Therefore the link between ozone associated asthma morbidity may be DCs. We hypothesize ozone exposure may site specifically alter DC phenotypes, numbers, and functions thus altering the overall lung immune phenotype. Herein, we demonstrate ozone exposure induces site-specific DC accumulation of the CD11b+SIRPa;+ and CD11b-CD103+ phenotype within the trachea and mediastinal lymph nodes (MLN). Such accumulation could result in increased antigen presentation during allergen co-exposures. Within the MLN, DC costimulatory molecules were down-regulated, however, an increase in the total T cell population was observed. These data indicate exposure alone, while able to induce airway DC recruitment and lymph node migration, does not initiate full DC maturation. We further hypothesize the T cell number increase may be due to Foxp3+ T regulatory cell expansion, which could explain both costimulatory molecule down-regulation and absence of adaptive immune responses after ozone exposure. To further understand the mechanisms by which ozone affected DC function, we developed an in vitro exposure system using bone-marrow derived DC covered by a thin film (modeled after epithelial lining fluid), which are exposed to ozone, and then analyzed for co-stimulatory molecule expression. Similar to our in vivo studies, reductions in CD80 expression were seen only when solutions contained lipid and protein, or lipid alone. Attempts were also made using a transgenic mouse model allowing CD11c+ cell depletion to determine what role DCs play in controlling the innate immune response after exposure, however this model proved non-reliable. Together, these data support a new mechanism for linking DC, asthma, and ozone exposure through site-specific DC accumulation and provide further understanding how ozone exposure alone alters DC function.

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