Abstract
Background Leukotriene E4 (LTE4) is the final biologically active and bronchoconstrictive cysteinyl leukotriene (CysLT). There is expression of CysLT receptors on mast cells, suggesting that CysLTs might regulate mast cell mediator release.
Objective We tested this hypothesis by evaluating if inhaled LTE4 affected urinary excretion of the main metabolites of the mast cell mediator PGD2 in subjects with asthma. Data were obtained both during control conditions and after treatment with the potent CysLT1 receptor antagonist montelukast.
Methods Fourteen subjects with mild asthma received montelukast 20mg bid or placebo for 5-7 days in a randomized, double blind, crossover study. At the end of every treatment period a LTE4 inhalation challenge was performed and urine was collected before, during, and at hourly intervals after the challenge for up to 4 hours. Urinary excretion of the PGD2 metabolite 11β-PGF2a was measured using enzyme immunoassay (EIA).
Results There was a significant increase in the urinary excretion of 11β-PGF2a following LTE4 induced bronchoconstriction (mean SEM 58.5 ± 6.4 baseline vs 383 ± 120 peak ng.mmol creatinine-1, p=0.016). This effect was completely abolished after treatment with montelukast.
Conclusion This is the first in vivo demonstration that inhalation of LTE4 induces increased urinary excretion of the main metabolites of the bronchoconstrictive mast cell-derived mediator PGD2. The effect was mediated through the CysLT1 receptor. Our data indicate that CysLTs should be reclassified as dual bronchoconstrictors, combining direct effects on smooth muscle with indirect effects promoting release of further mast cell mediators.
- Copyright ©the authors 2016