Ozone‐induced eosinophil recruitment to airways is altered by antigen sensitization and tumor necrosis factor‐α blockade

• Published in: Physiological reports Vol. 5; no. 24; pp. e13538 - n/a
• Main Authors: Wicher, Sarah A., Lawson, Katy L., Jacoby, David B., Fryer, Allison D., Drake, Matthew G.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.12.2017; John Wiley and Sons Inc
• Subjects: Airway; Alveoli; Animals; Asthma; Asthma - etiology; Asthma - immunology; Asthma - pathology; Autonomic Nervous System; Bronchus; Cell Movement; eosinophil; Eosinophils - drug effects; Eosinophils - immunology; Eosinophils - physiology; Etanercept; Etanercept - pharmacology; Female; Guinea Pigs; Immunology; Immunosuppressive Agents - pharmacology; Leukocytes (eosinophilic); Mucous membrane; Necrosis; nerve; Nerves; Original Research; Ovalbumin; Ozone; Ozone - adverse effects; Parasympathetic nervous system; Respiratory Conditions Disorder and Diseases; Respiratory Mucosa - immunology; Respiratory Mucosa - pathology; Respiratory System - innervation; Respiratory tract; TNF α; Toxins, Pollutants and Chemical Agents; Tumor necrosis factor; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; TNF α; asthma; eosinophil; Airway; ozone; nerve
• ISSN: 2051-817X; 2051-817X
• DOI: 10.14814/phy2.13538

Ozone is an atmospheric pollutant that causes lung inflammation and airway hyperresponsiveness. Ozone's effects occur in two distinct phases that are mediated by different populations of eosinophils. In the acute phase 1 day after exposure, mature airway‐resident eosinophils alter parasympathetic nerve function that results in airway hyperresponsiveness. At this time point, the severity of hyperresponsiveness correlates with the number of eosinophils in close proximity to airway nerves, but not with eosinophils in bronchoalveolar lavage. Three days later, newly divided eosinophils are recruited to airways by a tumor necrosis factor‐α‐dependent mechanism. These new eosinophils paradoxically attenuate ozone‐induced airway hyperresponsiveness. Ozone's effects on airway tissue eosinophils and nerve‐associated eosinophils 3 days after exposure are unknown. Thus, we tested ozone's effects on eosinophils in airway subepithelium and around airway nerves 1 and 3 days after ozone in nonsensitized and ovalbumin‐sensitized guinea pigs with or without the tumor necrosis factor‐α antagonist, etanercept, and compared changes in eosinophils with ozone‐induced airway hyperresponsiveness. More eosinophils were present in small, noncartilaginous airways and along small airway nerves compared to large cartilaginous airways in all treatment groups. The number of airway and nerve‐associated eosinophils were unaffected 1 day after ozone exposure, whereas significantly fewer airway eosinophils were present 3 days later. Airway and nerve‐associated eosinophils were also decreased in small airways 3 days after ozone in sensitized animals. These changes were blocked by etanercept. Airway eosinophils, but not nerve‐associated or bronchoalveolar lavage eosinophils correlated with airway hyperresponsiveness 3 days after ozone. Our findings indicate ozone causes persistent alterations in airway eosinophils and reinforce the importance of characterizing eosinophils’ effects within distinct airway compartments. Ozone causes neuronally mediated airway hyperresponsiveness 1 day after exposure that is eosinophil‐dependent. However, eosinophils paradoxically attenuate airway hyperresponsiveness by day 3. We found that the number of eosinophils in airway walls, but not eosinophils associated with airway nerves, correlates with airway hyperresponsiveness, and is altered by sensitization and TNF‐alpha antagonists.