Ciliary responsiveness in allergic and nonallergic airways.
Allergic asthma is associated with airway (smooth muscle) hyperresponsiveness to several chemical mediators of anaphylaxis; however, it is not known whether this is accompanied by mucociliary hyperresponsiveness. The purpose of this study was therefore to determine if airway ciliary activity, a component function of mucociliary clearance, exhibits exaggerated responses to prostaglandin E1 (PGE1), prostaglandin E2 (PGE2), and leukotriene D4 (LTD4) in allergic sheep when compared with nonallergic sheep, and the effects of LTD4 are direct or involve the generation of cyclooxygenase products of arachidonate metabolism. Ciliary beat frequency (CBF) was measured in a perfusion chamber with a microscopic technique using tracheal epithelial cells obtained from brushing of "allergic" (positive cutaneous reaction and previous bronchospastic response to inhaled specific antigen) and "nonallergic" (negative cutaneous reaction, no previous inhalation challenge with antigen) sheep. Mean base-line CBF was not different among the groups; PGE1, PGE2, and LTD4 induced dose-dependent increases in CBF, and these increases were not different in allergic and nonallergic sheep. At the highest agonist concentration the mean increase in CBF from base line varied between 13 and 16% (P less than 0.05). The ciliostimulatory effect of LTD4 was significantly blunted by both the sulfidopeptide leukotriene antagonist FPL-55712 and the cyclooxygenase inhibitor indomethacin. These results suggest that allergic sheep fail to exhibit ciliary hyperresponsiveness to selected chemical mediators of anaphylaxis and the ciliostimulatory effect of LTD4 depends on the activation of cyclooxygenase and possibly the generation of prostaglandins.
Wanner
A
A
Sielczak
M
M
Mella
J F
JF
Abraham
W M
WM
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D001200:Ascaris / Q000276:immunology; D001249:Asthma / Q000503:physiopathology; D002923:Cilia / Q000187:drug effects / Q000502:physiology; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006967:Hypersensitivity / Q000276:immunology / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D009994:Osmolar Concentration; D011458:Prostaglandins E / Q000494:pharmacology; D012016:Reference Values; D013189:SRS-A / Q000494:pharmacology; D012756:Sheep; D014132:Trachea / Q000473:pathology / Q000503:physiopathology*
D011458:Prostaglandins E; D013189:SRS-A; D000527:Alprostadil; D015232:Dinoprostone; D007213:Indomethacin