| Abstract: | Immunologic degranulation of airway mast cells after antigen inhalation produces early and late airway obstructions in allergic sheep. In this study we determined whether nonimmunologic degranulation of airway mast cells by inhalation of compound 48/80 had similar effects. In five sheep, pulmonary flow resistance (RL), thoracic gas volume (Vtg), and arterial O2 tension (Pao2) were determined prior to and at predetermined times after inhalation of 48/80 aerosol. Immediately after challenge mean specific lung resistance (sRL = RL X Vtg) increased by 259% and mean Pao2 decreased by 29%. All values returned to normal by 3 h. By 5-h postchallenge sRL again increased significantly; this second increase in sRL (92% above base line) was maximal at 7 h and was accompanied by a 17% drop in Pao2. In these same sheep inhalation of Ascaris suum antigen produced comparable early changes in sRL, but the onset of the late response was somewhat delayed and more pronounced. In a second group of sheep (n = 5), pretreatment with the mast cell stabilizer cromolyn sodium prevented both early and late responses by compound 48/80. Pretreatment with the histamine H1-antagonist chlorpheniramine had no significant effect on either response, whereas pretreatment with FPL 55712, an antagonist of slow-reacting substance of anaphylaxis (SRS-A), slightly but not significantly attenuated the early response and completely prevented the late response. We conclude that, like immunologic stimuli, nonimmunologic mast cell degranulation produces early and late bronchial obstructions in allergic sheep; that these responses are mediator dependent; and that while histamine and SRS-A contribute to the early response, it is the early appearance of SRS-A which is an important prerequisite for the late response. |
