We studied the effects of repeated exposures of antigen on 1) airway reactivity to mediators of anaphylaxis and 2) immediate response to the antigen. Seven antigen-sensitive sheep were exposed to aerosols of Ascaris suum antigen 5 times biweekly; a control group of seven sheep underwent the same exposure regimen with saline vehicle. Sheep were assigned to experimental (Ascaris) or control groups so the distribution of animals with regard to bronchial reactivity to mediators was about the same. Airway reactivity was assessed by determining the effects of aerosolized histamine (10-1,000 μg), prostaglandin F(2α) (PGF(2α), 10-300 μg), and a stable analogue of thromboxane A2 (U-46619, 1-100 μg) on lung resistance (RL) and dynamic lung compliance (Cdyn). Before treatment, experimental and control groups showed similar changes in RL and Cdyn, with analogue>histamine>PGF(2α). At the highest dose of each antagonist, mean increases in RL were 50, 123, and 29% respectively, and mean decreases in Cdyn were 21, 45, and 29%. During the first 15-min exposures to antigen aerosol, mean RL had increased by 125% and Cdyn decreased by 38% of base-line values; hyperinflation following the exposures reduced the changes to 56 and 31%, respectively. Changes in RL and Cdyn during the final antigen exposures and following postexposure hyperinflation were reduced significantly (P<0.05) compared with the initial exposures, Base-line RL and Cdyn before and after the exposures to antigen or saline were not significantly different. Airway reactivity to histamine, PGF(2α), or analogue was not significantly altered in these atropinized animals over the range of doses studied.Histological examination demonstrated that sheep exposed to antigen had significantly lower pulmonary mast cell densities than did saline-exposed sheep (P<0.05). These experiments demonstrate that bronchopulmonary responses to antigen inhalation were reduced after repeated antigen challenge. Diminished response occurred independent of changes in nonspecific airways reactivity and may have been due, in part, to reduced pulmonary mast cell density.
ASJC Scopus subject areas
- Physiology (medical)