title: Central role of cyclooxygenase in the response of canine peripheral airways to antigen.
abstract: We studied the effects of antigen aerosol challenge on the airways of the canine peripheral lung and examined the roles of cyclooxygenase products, histamine, and cholinergic activity in the responses. One-minute deliveries of 1:10,000 or 1:100,000 concentrations of Ascaris suum antigen aerosol through a wedged bronchoscope resulted in mean maximal increases in collateral system resistance (Rcs) of 415 and 177%, respectively, after 4-8 min. Repeated antigen challenge (1:100,000) resulted in significantly decreased responsiveness to antigen after the initial exposure (P less than 0.005). Bronchoalveolar lavage fluid obtained from the isolated, challenged segment had a significant increase in mean (+/- SE) prostaglandin D2 (PGD2) concentration vs. control (222.0 +/- 65.3 vs. 72.7 +/- 19.5 pg/ml; P less than 0.05); histamine concentrations were variable and not significantly different (4.1 +/- 2.6 vs. 1.2 +/- 0.2 ng/ml; P greater than 0.05). In nine experiments, cyclooxygenase inhibition significantly attenuated the antigen-induced increase in Rcs by 53.4% (P less than 0.001), and the concentration of PGD2 in lavage fluid was reduced by 96.0% (P less than 0.01). Blockade of histamine H1-receptors (n = 8) or cholinergic receptors (n = 7) did not significantly affect the airway response (P greater than 0.05). These data indicate that the canine peripheral lung responds in a dose-dependent manner to antigen aerosol challenge and exhibits characteristics of antigen tachyphylaxis. Results also suggest that cyclooxygenase products play a central role in the acute bronchoconstrictive response of the lung periphery.
mesh_terms: D000336:Aerosols; D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D000947:Antigens, Helminth / Q000276:immunology; D001200:Ascaris / Q000276:immunology; D002744:Chlorpheniramine / Q000494:pharmacology; D004285:Dogs; D006636:Histamine Release; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage; D015230:Prostaglandin D2; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011457:Prostaglandins D / Q000032:analysis; D007507:Therapeutic Irrigation
chemical_list: D000336:Aerosols; D000941:Antigens; D000947:Antigens, Helminth; D011457:Prostaglandins D; D002744:Chlorpheniramine; D010047:Ovalbumin; D011451:Prostaglandin-Endoperoxide Synthases; D015230:Prostaglandin D2; D007213:Indomethacin