[The role of neutrophils in airway hyperresponsiveness in dogs after ozone exposure]

To determine whether neutrophils are involved in airway hyperresponsiveness after ozone exposure, we studied the effect of neutrophil depletion by cyclophosphamide treatment on ozone-induced airway hyperresponsiveness in seven dogs. Airway responsiveness to inhaled methacholine was determined by modified Astograph (7 Hz oscillation method), and the numbers of neutrophils in the peripheral blood, total cell counts and differential cell counts in BALF were measured before and after ozone exposure, and after ozone exposure of dogs undergoing cyclophosphamide treatment. Ozone exposure was carried out for 2 hrs at an ozone level of 3.07 +/- 0.01 ppm (mean +/- SE), and cyclophosphamide (10 mg/kg) was given intravenously daily for five days starting six days before ozone exposure. There was a significant increase in airway responsiveness to inhaled methacholine after ozone exposure in the seven dogs (p less than 0.001), and the numbers of neutrophils in the peripheral blood and the neutrophil counts in BALF increased significantly after ozone exposure (p less than 0.01). After ozone exposure of dogs undergoing cyclophosphamide treatment, the numbers of neutrophils in the peripheral blood decreased significantly (p less than 0.001) and the neutrophil counts in BALF did not increase, but the airway responsiveness to inhaled methacholine increased significantly (p less than 0.01). There was no significant correlation between the degree of the increase in airway responsiveness and the degree of the increase in neutrophil counts in BALF after ozone exposure. These results suggest that neutrophil infiltration into the airway is not necessary for an increase in airway responsiveness after ozone exposure in dogs.