Bronchial hyperresponsiveness and cellular infiltration in the lung of guinea-pigs sensitized and challenged by aerosol

Abstract

We have studied the development of airway hyperresponsiveness and the pulmonary cell infiltration in a guinea-pig model in which both initial sensitization and subsequent exposure to the antigen were performed by aerosol. Enhanced bronchopulmonary response to aerosol administration of acetylcholine (ACh) and 5-hydroxytryptamine (5-HT) was observed 3-4 hr and 18-24 hr after antigen exposure of sensitized animals. In contrast, when ACh and 5-HT were administered intravenously 3-4 hr after the challenge, no significant alteration of the dose-response curves was observed. However, 18-24 hr after antigen challenge, a marked leftward shift of the dose-response curve was observed on intravenous injection of ACh or 5-HT. The increased bronchial reactivity to aerosolized ACh in sensitized and challenged guinea-pigs reached a maximum by days 2-4, was still significantly increased at day 5 and returned to the basal value by day 8. No further alteration of the dose-related bronchopulmonary response to aerosol or intravenous administration of ACh was recorded 24 hr after a second antigen challenge, performed 8 days after the initial one. The analysis of bronchoalveolar lavage fluids showed a significant increase in the number of polymorphonuclear neutrophils 3-4 hr after the exposure of sensitized animals to the antigen, which was also associated with a significant eosinophilia at 18-24 hr. Histological examination of lung specimens obtained from animals 3-4 hr following challenge demonstrated eosinophil infiltration in the peribronchial regions and bronchial walls, as well as within the epithelium. Furthermore, as compared to time 3-4 hr, less eosinophils in the peribronchial area and submucosa were counted 24 hr after antigen challenge. However, a role of eosinophil-derived products in the development of bronchial hyperresponsivenss in this experimental model remains to be established.