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
To investigate whether allergen-induced changes in the 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 [CysLT1] 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 CysLT1 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 CysLT1 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.


CONCLUSIONS
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.
Parameswaran
Krishnan
K
Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Department of Medicine, McMaster University, Hamilton, Canada.
Liang
Hong
H
Fanat
Adrian
A
Watson
Richard
R
Snider
Denis P
DP
O'Byrne
Paul M
PM
D000328:Adult; D000485:Allergens / Q000009:adverse effects / Q000276:immunology; D001249:Asthma / Q000188:drug therapy / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000276:immunology; D002452:Cell Count; D002630:Chemotactic Factors / Q000276:immunology; D002867:Chromones / Q000494:pharmacology* / Q000627:therapeutic use; D018592:Cross-Over Studies; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004311:Double-Blind Method; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D008565:Membrane Proteins / Q000187:drug effects / Q000276:immunology*; D008875:Middle Aged; D018077:Receptors, Leukotriene / Q000187:drug effects / Q000276:immunology*; D013183:Sputum / Q000737:chemistry / Q000276:immunology
D000485:Allergens; D002630:Chemotactic Factors; D002867:Chromones; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D018077:Receptors, Leukotriene; C083169:leukotriene D4 receptor; C047681:pranlukast