Role for cysteinyl leukotrienes in allergen-induced change in circulating dendritic cell number in asthma

Background: Dendritic cells are important antigen-presenting cells. After an allergen inhalation, their numbers rapidly decrease in circulation and increase in the airway mucosa. Objective: number of circulating dendritic cells are mediated by cysteinyl leukotrienes. Methods: In a randomized, double-blind, crossover study, we examined the effects of 2 weeks of treatment with pranlukast (a cysteinyl leukotriene 1 [CysLT(1)] receptor antagonist) 300 mg twice daily and placebo on allergen-induced changes in airway responses and circulating dendritic cells in 15 subjects with mild asthma. We examined by flow cytometry, before and at 3 hours and 24 hours after allergen inhalation, the proportion of myeloid (CD33(+)) and plasmacytoid (CD123(+)) dendritic cells (HLA-DR+, CD14(-), CD16(-)) among all peripheral blood mononuclear cells. The fraction of dendritic cells expressing CysLT(1) receptor was also determined. Results: Compared with placebo, pranlukast significantly attenuated both the maximum early (by 55%) and the late (by 39%) asthma responses, the allergen-induced methacholine airway hyperresponsiveness, and the increase in macrophage inflammatory protein 1alpha and 3alpha in induced sputum. A significantly greater proportion of CD33(+) cells (55%) expressed CysLT(1) receptor compared with CD123(+) cells (11%). Consistent with this, pranlukast prevented the allergen-induced decrease in CD33(+) dendritic cells at 3 hours postallergen (mean Delta from baseline, +4.4%) compared with placebo (mean Delta, -8.4; P < .05), but not CD123(+) cells. Conclusion: Pretreatment with pranlukast attenuated allergen-induced airway responses and the decrease in circulating myeloid dendritic cells, demonstrating a novel role of cysteinyl leukotrienes in dendritic cell trafficking.