Blockade of eosinophil migration by 5-lipoxygenase and cyclooxygenase inhibition in explanted guinea pig trachealis.
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.
Muñoz
N M
NM
Department of Medicine, University of Chicago, Illinois 60637.
Leff
A R
AR
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000081:Acetamides / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004804:Eosinophils / Q000502:physiology*; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D016859:Lipoxygenase Inhibitors; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010647:Phenyl Ethers; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014132:Trachea / Q000166:cytology*
D000081:Acetamides; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D010647:Phenyl Ethers; D011450:Prostaglandin Endoperoxides, Synthetic; C068663:N-hydroxy-N-(1-(4-(phenylmethoxy)phenyl)ethyl)-acetamide; D013928:Thromboxane A2; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001094:Arachidonate 5-Lipoxygenase; D000109:Acetylcholine; D007213:Indomethacin