June 2012

Document Type


Degree Name



Dept. of Cell and Developmental Biology


Oregon Health & Science University


Asthma is a chronic inflammatory disease of the lung and a significant health burden. Airway sensory neurons in asthma malfunction and contribute to airway hyperreactivity. The upstream changes to neuron structure and the inciting factors behind sensory dysfunction are unknown due to obstacles in characterizing airway innervation. This project aims to offer insight into sensory neuroplasticity, or how sensory neurons change in asthma. I initially hypothesized that a new method of capturing and quantifying nerves would more accurately and comprehensively measure whole organ innervation. Thus I initially developed a new method permitting the visualization of whole airway innervation and computerized quantification of nerve branching and nerve density (Chapter 3). I then hypothesized that in asthma an inflammatory cell called the eosinophil is important for airway neuroplasticity. Thus I used this new nerve modeling method to show that in a model of chronic allergic inflammatory asthma but not acute allergic inflammatory asthma, increased eosinophils in the airway results in branched outgrowth of airway epithelial nerves (Chapter 4). Furthermore, I showed this branched outgrowth was associated with increased reflex bronchoconstriction, a physiologic characteristic of asthma mediated by airway nerves (Chapter 4). I subsequently used transgenic mice lacking eosinophils to show they were necessary both for sensory nerve branched outgrowth and increased reflex bronchoconstriction (Chapter 4). Neuronal hypersensitivity and dysfunction in atopic dermatitis, an itchy skin disease, is also associated with changes in nerve density. I hypothesized that eosinophils were important for nerve structural changes. I utilized the same computer modeling approach and found opposite neurotrophic or neuropathic effects caused by eosinophils in a chronic versus acute dermatitis model (Chapter 5). In co-culture experiments, I showed eosinophils produce neurotrophic effects on sensory nerves measured as increased nerve length. Overall this dissertation shows a new technique for quantification of nerve structure and uses this approach to demonstrate that eosinophils in inflammatory disease are capable of causing neurotrophic and neuropathic neuroplasticity. Moreover, neuroplasticity caused by eosinophils is associated a major cause of morbidity in asthma, increased reflex bronchoconstriction. Thus the current dissertation describes eosinophil neuroimmune interactions important for pathogenesis and symptom manifestation in allergic airway and skin diseases.




School of Medicine



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