Allergen-induced oxygen radical release from bronchoalveolar lavage cells and airway hyperresponsiveness in dogs.
Allergen inhalation causes airway hyperresponsiveness and airway inflammation in dogs. The purpose of this study was to determine whether allergen-induced airway hyperresponsiveness is associated with increases in oxygen radical production from bronchoalveolar lavage (BAL) cells. A group of 10 random-source dogs were studied twice, 4 wk apart. On each occasion, acetylcholine (ACh) airway responsiveness was measured before and 24 h after inhalation of Ascaris suum or its diluent, followed by BAL. The response to ACh was expressed as the concentration causing an increase in lung resistance of 5 cm H2/O/L/s above baseline. Spontaneous and phorbol myristate acetate (PMA)-stimulated (2.4 mumol/L) oxygen radical release were measured, for 10 min each, from washed BAL cells (4 x 10(6) cells/ml) by luminol-enhanced chemiluminescence in a luminometer at 37 degrees C. Superoxide anion production was measured using a cytochrome c assay. Allergen inhalation caused bronchoconstriction, airway inflammation, and airway hyperresponsiveness. The acetylcholine provocative concentration fell from 7.47 mg/ml (% SEM 1.61) before to 1.23 mg/ml (% SEM 1.62) after allergen (p < 0.0001). Allergen inhalation significantly increased absolute neutrophil (p = 0.03) and eosinophil (p = 0.02) counts in BAL. Spontaneous (p < 0.0003) and PMA-stimulated (p < 0.0005) chemiluminescence and superoxide anion production (p = 0.039) were increased after allergen inhalation. The allergen-induced increases in chemiluminescence were significantly correlated with the increases in ACh airway hyperresponsiveness (r = 0.75, p < 0.012). These results indicate that inhaled allergen increases oxygen radical release from bronchoalveolar lavage cells and supports the hypothesis that oxygen radicals are important in causing allergen-induced airway hyperresponsiveness.
Stevens
W H
WH
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Inman
M D
MD
Wattie
J
J
O'Byrne
P M
PM
D000109:Acetylcholine / Q000494:pharmacology; D000403:Airway Resistance; D000485:Allergens; D000818:Animals; D017165:Ascaris suum; D016535:Bronchial Hyperreactivity / Q000378:metabolism*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D004285:Dogs; D004804:Eosinophils; D007958:Leukocyte Count; D008163:Luminescent Measurements; D009504:Neutrophils; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000485:Allergens; D013481:Superoxides; D000109:Acetylcholine; D013755:Tetradecanoylphorbol Acetate