Project Leader: Greg Smith

Inhalation exposure to ozone disrupts respiratory innate immune system function causing increased vulnerability to infection and inappropriate responses to allergens. The respiratory innate immune system includes resident airway leukocytes (e.g. alveolar macrophages) and epithelial cells that line the alveolar surface and airways. Airway innate immune functions include the recognition and removal of pathogens and damaged cells, as well as the maintenance of a robust physical barrier to foreign material. Ozone decreases alveolar macrophage mediated phagocytosis and bactericidal activity and increases pro-inflammatory cytokine release from both macrophages and epithelial cells. Additionally, ozone “loosens” the tight junctions between airway epithelial cells promoting lung inflammation and increasing the flux of foreign material into the pulmonary interstitium and circulation. Epithelial cells and alveolar macrophages normally communicate with each other to regulate their innate immune functions. We hypothesize that ozone causes innate immune dysfunction by disrupting airway cell communication, specifically communication through extracellular vesicles (EVs). EVs are nano-scale lipid membrane bound particles containing biologically active cargo. To investigate our hypothesis, we are examining ozone-induced airway EV-release and ozone-induced alterations in EV-cargo and determining the effects of altered airway EVs on airway alveolar macrophage and epithelial cell function. The overall goal of this work is to improve our understanding of the mechanisms by which ozone-impairs airway innate immune function.