Leukotriene synthesis inhibition and anti-ige challenge of human lung parenchyma

• Published in: Life sciences (1973) 1996, Vol.59 (13), p.PL213-PL219
• Main Authors: Gorenne, I., Alaoui, H.Sosse, Gascard, J.P., Labat, C., Norel, X., De Montpreville, V., Brink, C.
• Format: Article
• Language: English
• Subjects: anti-IgE; human lung parenchyma; Humans; Immunoglobulin E - immunology; Indoles - pharmacology; Indomethacin - pharmacology; Kinetics; Leukotriene Antagonists; leukotriene E 4; leukotriene synthesis inhibitors; Leukotrienes - biosynthesis; Leukotrienes - metabolism; Lung - drug effects; Lung - immunology; Protein Synthesis Inhibitors - pharmacology; Quinolines - pharmacology
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/0024-3205(96)00426-2

The leukotriene (LT) synthesis inhibitors BAY x1005 and MK-886 were evaluated in human lung parenchyma challenged with an anti-IgE. The anti-IgE-induced LTE 4 release was time- and dose-dependent. Treatment of the parenchyma with indomethacin (3 μM) prior to anti- IgE challenge inhibited the 6-keto prostaglandin F 1α (6-keto PGF 1α) release and enhanced (36%) the quantities of LTE 4 detected during IgE-stimulations. BAY x1005 and MK-886 were assessed in the presence of indomethacin (3 μM) and the IC 50 values for both inhibitors were similar (0.13 μM). BAY x1005 (1 μM) produced the same percent of inhibition of anti-IgE-induced LTE 4 release in the presence or absence of indomethacin. BAY x1005 (1 μM) did not alter the 6-keto PGF 1α release during anti-IgE challenge. The results indicate that BAY x1005 and MK-886 are potent inhibitors of LT synthesis when human lung parenchyma were stimulated by an anti-IgE.