VIRUS-INDUCED CHANGES IN AIRWAY RESPONSIVENESS, MORPHOLOGY, AND HISTAMINE LEVELS IN GUINEA-PIGS

A significant increase in airway responsiveness to histamine was observed in vitro and in vivo 4 days after intratracheal inoculation of parainfluenza Type 3 (PI-3) virus to guinea pigs. Light microscopic and ultrastructural examination of the central airways of animals inoculated with virus revealed stratification of the epithelial lining, with pronounced loss of cilia and granule-depleted goblet cells. In the peripheral airways, typical lesions of patchy alveolitis and bronchiolitis were found. The alveolar epithelium often lacked Type I alveolar cells and was lined merely by cells containing osmiophilic lamellar bodies typical of Type II alveolar cells. PI-3 virus inoculation resulted in a reduction in the number of airway mucosal mast cells, particularly in the bronchioles, and in a change of density of the granules of mast cells. Further, a significant rise (100%) in histamine concentration was observed in lung lavage fluid after virus inoculation. The prostaglandin E2 (PGE2) content in the lavage fluid was not changed. After stimulation with histamine, the tracheae of animals inoculated with control solution or PI-3 virus produced similar amounts of PGE2. These data indicate that PI-3 virus activates airway mast cells and increases the histamine content in the respiratory tract. Neither the virus-induced lung damage nor the increased levels of histamine in the airways influence the release of the epithelially derived relaxing factor PGE2. It is suggested that mast cell-derived products, in particular histamine, are involved in virus-induced airway hyperresponsiveness.