Ozone causes vagally-mediated airway hyperreactivity and recruits inflammatory cells, including eosinophils, to lungs where they mediate ozone-induced hyperreactivity one day after exposure, but are paradoxically protective three days later. To test the role of newly divided eosinophils in ozone-induced airway hyperreactivity in sensitized and non-sensitized guinea pigs. Non-sensitized and sensitized guinea pigs were treated with 5-bromo-2-deoxyuridine (BrdU) to label newly divided cells and were exposed to air or ozone for 4 hours. One or three days later, vagally-induced bronchoconstriction was measured and inflammatory cells harvested from bone marrow, blood, and bronchoalveolar lavage. Ozone induced eosinophil hematopoiesis. One day post ozone, mature eosinophils dominate the inflammatory response and potentiate vagally-induced bronchoconstriction. However, by three days, newly divided eosinophils have reached the lungs where they inhibit ozone-induced airway hyperreactivity, since depleting them with AbIL-5 or a TNFα antagonist, worsened vagally-induced bronchoconstriction. In sensitized guinea pigs, both ozone-induced eosinophil hematopoiesis and subsequent recruitment of newly divided eosinophils to lungs three days later failed to occur. Thus, mature eosinophils dominated the ozone-induced inflammatory response in sensitized guinea pigs. Depleting these mature eosinophils prevented ozone-induced airway hyperreactivity in sensitized animals. Ozone induces eosinophil hematopoiesis and recruitment to lungs where three days later, newly divided eosinophils attenuate vagally-mediated hyperreactivity. Ozone-induced hematopoiesis of beneficial eosinophils is blocked by a TNFα antagonist, or by prior sensitization. In these animals, mature eosinophils are associated with hyperreactivity. Thus, interventions targeting eosinophils, while beneficial in atopic individuals, may delay resolution of airway hyperreactivity in non-atopic individuals.
- Eosinophil hematopoiesis
- Airway hyperreactivity
- Allergic Sensitization
- Copyright © 2016, American Journal of Physiology-Lung Cellular and Molecular Physiology