Eosinophil-mediated Sensory Neuroplasticity in Asthma

Oregon Health & Science University, Portland OR

Investigators

Linked publications & trials

Abstract

? DESCRIPTION (provided by applicant): Sensory nerves narrow airways in response to inhaled substances. Patients with asthma exhibit enhanced sensitivity and reactivity to inhaled stimuli, leading to life-threatening bronchoconstriction and symptoms such as shortness of breath and chest tightness. The mechanisms of airway nerve hyperreactivity are unclear and represent a potential therapeutic target. Eosinophils accumulate within the airways of asthmatic patients and interact with nerves. Eosinophils also increase cultured sensory nerve growth. The goal of this project is to determine if eosinophils cause airway hyperreactivity by regulating sensory nerve morphology, as well as neurotransmitter and receptor expression. This project proposes to use whole-mount immunostaining, tissue optical clearing, laser-scanning confocal microscopy, and digitized nerve modeling to characterize how eosinophils regulate nerve morphology and neurotransmitter content in murine models of asthma. Measurements of lung resistance in mice treated with selective pharmacologic antagonists will determine how eosinophil-mediated sensory neuroplasticity promotes airway hyperreactivity. This project also proposes to co- culture primary human sensory neurons with eosinophils to determine if eosinophils increase expression of select neurotransmitters and receptors. Taken together, achieving the goals of this proposal will increase understanding of how eosinophils promote airway nerve dysfunction in asthmatic patients.