Effect of nedocromil sodium on sulfidopeptide leukotrienes-stimulated human alveolar macrophages in asthma.
Alveolar macrophages (AM) may take part in the amplification of the inflammatory mechanism involved in asthma. During an asthma attack, mast cells and eosinophils release arachidonic acid derivative mediators of inflammation such as sulfidopeptide leukotrienes. Among them, LTC4 has been shown to be present in bronchoalveolar fluid. In asthmatic patients, we showed that the ability of AM to transform LTC4 into its derivatives LTD4 and LTE4 was related to the intensity of the local inflammation observed during endoscopy. AM from asthmatics incubated in the presence of LTC4 or LTE4, generated LTB4 and 5-HETE, which are potent chemoattractants. Nedocromil sodium (10(-4) M) decreased LTB4 releasability and intracellular 5-HETE concentrations in zymosan-stimulated AM from asthmatic patients, and was shown to decrease the LTC4 or LTE4-promoted formation of LTB4 and 5-HETE.
INSERM U 58, Montpellier, France.
T
T
Radeau
P
P
Godard
C
C
Chavis
F B
FB
Michel
B
B
Descomps
M
M
Damon
D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001249:Asthma / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D007975:Leukotriene B4 / Q000096:biosynthesis; D017999:Leukotriene E4; D015289:Leukotrienes / Q000378:metabolism / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D017835:Nedocromil; D015363:Quinolones / Q000494:pharmacology*; D013189:SRS-A / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013268:Stimulation, Chemical
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D015363:Quinolones; D013189:SRS-A; D017835:Nedocromil; D007975:Leukotriene B4; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D017999:Leukotriene E4