Source: Annual Congress 2001 - Molecular and cellular pathology of asthma
Disease area: Airway diseases

Abstract

Previous data showed that the accumulation of eosinophils in the airways may be leukotriene-dependent suggesting an effect of cysteinyl leukotrienes on eosinophil proliferation. In our study, the effects of LTD4 and LTE4 and diluent on peripheral blood eosinophil progenitors (EoB-CFU) were examined in atopic subjects. Methylcellulose cultures for peripheral blood EoB-CFU were counted after incubation with three different concentrations of LTD4 and LTE4 and suboptimal concentrations of GM-CSF, IL-3, IL-5. EoB-CFU increased only in the presence of LTD4 and GM-CSF. Greatest EoB-CFU numbers were observed with LTD4 10-7 M (17.27±]2.46 per 106 NAMC) compared to the diluent control (11.93±]2.01 per 106 NAMC) (p<0.0002). Smaller, but significant effects were observed for 10-6 M and 10-8 M LTD4. Subsequently, assays were performed in the presence of montelukast. In the LTD4 10-7 M conditions, montelukast reduced the colony formation in a dose-dependent manner from 1μM (11.0±]1.3) to 10μM (9.8±]1.7) to 50μM (9.5±]1.3) and the two last concentrations were significant as compared to the diluent control (13.0±]1.3) (p<0.05 and p<0.05, respectively). In conclusion, LTD4 but not LTE4 significantly promoted EoB colony formation stimulated by GM-CSF. The inhibition of this effect by montelukast suggests that this is a CysLT1 mediated effect.

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F. Braccioni, G. M. Gauvreau, S. C. Dorman, M. D. Inman, P. M. O'Byrne (Hamilton, Canada). A leukotriene antagonist, montelukast, reduces in vitro LTD4 increases in peripheral blood eosinophil progenitor colonies in atopic subjects. Eur Respir J 2001; 16: Suppl. 31, 3565

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