BLOCKADE OF EOSINOPHIL MIGRATION BY 5-LIPOXYGENASE AND CYCLOOXYGENASEINHIBITION IN EXPLANTED GUINEA-PIG TRACHEALIS

We studied the effects of 5-lipoxygenase inhibition with A63162 and cy clooxygenase inhibition with indomethacin (INDO) on 1) eosinophil chem otaxis and 2) airway narrowing caused by 10(-6) M formyl-Met-Leu-Phe ( fMLP) in tracheal explants from guinea pigs. Airway narrowing was asse ssed by calibrated micrometry, and eosinophil migration from the lamin a propria was expressed as number of eosinophils contained per 1 cm tr acheal segment. After 120 min, treatment with fMLP caused an increase in luminal eosinophils from 6,804 +/- 1,786 to 303,347 +/- 75,609 cell s (P < 0.001); airway diameter narrowed by 20.4 +/- 1.4%. In six prepa rations, A63162 inhibited airway narrowing caused by fMLP by 54.9 +/- 6.1%; INDO had a similar effect on airway diameter. However, maximal i nhibition of eosinophil migration was greater after 10(-6) M A63162 (3 8,393 +/- 7,434 cells; P < 0.001 vs. fMLP alone) than after treatment with 10(-5) M INDO (123,547 +/- 19,499 cells; P < 0.05). We demonstrat e a method that permits simultaneous measurements of eosinophil migrat ion and airway smooth muscle contraction in a guinea pig tracheal expl ant preparation. Our data suggest that eosinophil chemotaxis and chang es in internal airway diameter are caused by activation of both 5-lipo xygenase and cyclooxygenase pathways and that cell migration is indepe ndent of the physical consequences of airway smooth muscle contraction .