Early postnatal exposure to allergen and ozone leads to hyperinnervation of the pulmonary epithelium

Airway injury in infant monkeys exposed to ozone and/or house dust mite allergen (HDMA) is associated with a loss of epithelial innervation. In this study, we evaluated for persistence/recovery of the altered epithelial innervation. Thirty-day-old rhesus monkeys were exposed to repeated episodes of HDMA and/or ozone from 1 to 6 months of age and subsequently allowed to recover for 6 months in the absence of further ozone exposure and/or minimal HDMA challenge (sufficient to maintain allergen sensitization). At 1 year of age, nerve density in intrapulmonary airways was immunohistochemically evaluated using antibodies directed against protein gene product 9.5. Hyperinnervation and irregular epithelial nerve distribution was observed in both HDMA- and ozone-exposed groups; most prominent alterations were observed in animals exposed to HDMA plus ozone. Therefore, while adaptive mechanisms exist that re-establish epithelial innervation following cessation or diminution of exposure to HDMA and/or ozone, the recovery is associated with persistent proliferative mechanisms that result in hyperinnervation of the airways.