The effect of cysteinyl leukotrienes on growth of eosinophil progenitors from peripheral blood and bone marrow of atopic subjects

Background: The accumulation of eosinophils into the peripheral blood and airways of asthmatic subjects is, in part, dependent on cysteinyl leukotrienes (cysLTs). However, the effect of cysLTs on peripheral blood and bone marrow eosinophil progenitor cells in allergic subjects is not known. Objective: The purpose of this study was to evaluate the effects of leukotriene (LT) D-4 and LTE4 and the cysLT(1) receptor antagonist montelukast on peripheral blood and bone marrow cosinophil-basophil progenitor growth and development in atopic subjects. Methods: Semisolid methylcellulose cultures for peripheral blood and bone marrow eosinophil-basophil colonies were counted after incubation with or without addition of LTD4, LTE4, and montelukast in the presence of suboptimal concentrations of GM-CSF, IL-3, and IL-5. Results: Peripheral blood eosinophil-basophil colony-forming unit cultures grown in the presence of GM-CSF and bone marrow eosinophil-basophil colony-forming units grown in the presence of IL-5 were significantly increased by the addition of LTD4 (0.1 mumol/L). This increase was suppressed by montelukast (1 mumol/L). Conclusion: This study has demonstrated that the cysLT LTD4 can stimulate proliferation of eosinophil hematopoietic progenitor cells in the presence of eosinophilopoietic cytokines. The suppressive effect by montelukast demonstrates that this is a cysLT(1) receptor-mediated effect.