The actions of specific humoral mediators in the immediate response of the canine peripheral airways to antigen challenge are not well understood. Using a method which allows localized exposure of the peripheral lung to antigen, we investigated the role of locally released thromboxane A2 (TxA2) in the immediate response of collateral airways to aerosolized antigen. In dogs with native sensitivity to Ascaris suum antigen, resistance to flow through the collateral system (Rcs) was measured using a wedged bronchoscope technique. Local administration of antigen aerosol (25 μl, 1:10,000 dilution) produced a gradual increase in Rcs which reached a maximum of 365% of base line in 4-8 min. Analysis of bronchoalveolar lavage fluid obtained from the exposed segment at the peak of the response demonstrated significantly more TxB2 compared with control lavage samples (41.8 ± 7.8 pg/ml vs. 27.9 ± 8.3; P < 0.025). After inhibition of thromboxane synthase with UK-37,248 (2 mg/kg iv) or OKY-046 (5 mg/kg iv), the increase in Rcs was significantly reduced at 40 s (P < 0.001) and 2 min (P < 0.01) after antigen delivery, and the maximal increase was attenuated by 41% (P < 0.005). In contrast, the magnitude and time course of the airway response to aerosols of a stable thromboxane analog (U-46619) were not affected by blockade. Despite a similar attenuation (42%) of the maximal increase in Rcs by sodium meclofenamate (3 mg/kg iv), this cyclooxygenase inhibitor had no effect on the time course of the antigenic response. These data indicate that immediate antigenic responses of the canine peripheral airways are mediated in part by the local release of TxA2. The shift in time course following inhibition of thromboxane synthase suggests that this potent mediator may be synthesized and released early in the immunologic response.
ASJC Scopus subject areas
- Physiology (medical)