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Montelukast regulation of cysteinyl leukotriene release by blood eosinophils
Author(s) -
Chouinard François,
Langlois Anick,
Flamand Nicolas,
Ferland Claudine,
Laviolette Michel
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a183-a
Subject(s) - montelukast , leukotriene , leukotriene e4 , leukotriene c4 , chemistry , leukotriene d4 , leukotriene receptor , eosinophil , antagonist , pertussis toxin , receptor , arachidonate 5 lipoxygenase , receptor antagonist , inflammation , pharmacology , medicine , asthma , enzyme , biology , biochemistry , g protein , arachidonic acid
Cysteinyl leukotrienes (CysLT) (LTC4, LTD4 and LTE4) play major roles in asthma pathogenesis. Asthma is characterized by leukocyte infiltration in the bronchial mucosa, notably eosinophils (Eo), which are a main source of CysLT. Montelukast (MTK), a CysLT receptor antagonist used in the treatment of asthma, diminishes the inflammation caused by CysLT. In this study, we evaluated the effect of MTK on the calcium ionophore (A23187)‐induced LTC4 release in isolated Eo. Asthmatics' blood Eo (n = 4) were incubated with either MTK, the 5‐lipoxygenase‐activating‐protein antagonist MK‐0591, or Pertussis toxin (PTX), which inactivates Gαi‐proteins, putatively coupled to CysLT receptor. Eo were then stimulated with A23187 (100 nM). LTC4 levels were determined in cell‐free supernatants by enzyme‐linked immunoassay. MTK decreased LTC4 release by 10 to 80% in a dose‐dependent manner. This effect was significant at 1 and 10 μM (p<0.001). MK‐0591 (10 nM), used as positive control, decreased LTC4 release by 92% (p=0.01). PTX (25 ng/ml) decreased the LTC4 release by 30% (p=0.03); such an effect was not sufficient to support an inhibition of LTC4 autocrine stimulation by MTK. These data suggest that MTK decreases LTC4 release by a mechanism unrelated to CysLT receptor blockade. The molecular target involved in this inhibitory effect of MTK on LTC4 release remains to be unraveled.