AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 3 446-L454, Copyright © 1995 by American Physiological Society
Blockade of eosinophil migration by 5-lipoxygenase and cyclooxygenase inhibition in explanted guinea pig trachealis
N. M. Munoz and A. R. Leff
Department of Medicine, University of Chicago, Illinois 60637.
We studied the effects of 5-lipoxygenase inhibition with A63162 and
cyclooxygenase inhibition with indomethacin (INDO) on 1) eosinophil
chemotaxis and 2) airway narrowing caused by 10(-6) M formyl-Met-Leu-Phe
(fMLP) in tracheal explants from guinea pigs. Airway narrowing was assessed
by calibrated micrometry, and eosinophil migration from the lamina propria
was expressed as number of eosinophils contained per 1 cm tracheal segment.
After 120 min, treatment with fMLP caused an increase in luminal
eosinophils from 6,804 +/- 1,786 to 303,347 +/- 75,609 cells (P <
0.001); airway diameter narrowed by 20.4 +/- 1.4%. In six preparations,
A63162 inhibited airway narrowing caused by fMLP by 54.9 +/- 6.1%; INDO had
a similar effect on airway diameter. However, maximal inhibition of
eosinophil migration was greater after 10(-6) M A63162 (38,393 +/- 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 demonstrate a method that
permits simultaneous measurements of eosinophil migration and airway smooth
muscle contraction in a guinea pig tracheal explant preparation. Our data
suggest that eosinophil chemotaxis and changes in internal airway diameter
are caused by activation of both 5-lipoxygenase and cyclooxygenase pathways
and that cell migration is independent of the physical consequences of
airway smooth muscle contraction.
