Airway hyperresponsiveness after endotoxin inhalation depends on leukocyte infiltration

We have investigated the relationship between acute airway hyperresponsiveness and polymorphonuclear cell (PMN) migration in airways following saline or endotoxin (ET) aerosol inhalation in 63 guinea pigs. In 20 of these animals, granulocytopenia was induced by prior treatment with hydroxyurea (HU). Airway responsiveness (AR) to inhaled methacholine, together with leukocyte counts in bronchoalveolar lavage fluid (BALF) and in tracheal epithelium, was also examined before and at 30 min, 1, 3 and 6 hr after saline or ET inhalation. In saline inhalation groups, AR and PMN counts in BALF and in tracheal epithelium did not differ from control animals at any time points. However, in ET inhalation groups AR increased significantly at 1 and 3 hr and returned to the pre-exposure level at 6 hr. This period of hyperresponsiveness was associated with an increment of PMN migration into tracheal epithelium. However, the increment of PMN counts in BALF was delayed to 3 and 6 hr after ET. In HU treated animals, AR and PMN counts in BALF and in tracheal epithelium did not change during 6 hr after ET inhalation. These results suggest that the hyperresponsiveness induced by ET inhalation either depends upon PMN migration into the tracheal epithelium.