Increase in Luminal Mast Cell and Epithelial Damage May Account for Increased Airway Responsiveness after Viral Infection in Dogs

Abstract

To elucidate the mechanisms of airway hyperresponsiveness induced by viral infection, we examined histologically and analyzed bronchoalveolar lavage (BAL) fluid using dogs infected with influenza C and noninfected control dogs. Airway responsiveness was assessed as inhaled acetylcholine concentration required to increase pulmonary resistance by 5 cm H2O/L/s (ACh PC). Airway responsiveness was determined before and 2 wk after virus or vehicle inoculation in infected and control dogs, and BAL and histologic studies were performed after the final challenge. Differential cell numbers and histamine concentration were determined in the BAL fluids of both groups. The ACh PC of control dogs did not change with the vehicle inoculation. However, that of infected dogs decreased two to five times as much as their initial value with viral infection. Histologic studies revealed diffuse epithelial damage in the central airways of infected dogs, but infiltrated cell counts within the airway tissue of both groups were not significantly different. From BAL analysis, mast cell number and the histamine concentration of infected dogs increased significantly compared with those of control dogs (3.1 +/- 0.4 x 10(5) versus 0.9 +/- 0.3 x 10(5) cells/ml and 7.3 +/- 1.7 versus 1.9 +/- 0.5 ng/ml, respectively). Luminal mast cell number and epithelial damage score in each dog was correlated with the increase in airway responsiveness. These findings indicate that airway inflammation in virus-induced hyperreactive dogs is characterized by epithelial damage and luminal increase in mast cells and related mediators, and these changes may be related to the appearance of virus-induced airway hyperreactivity.