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

• Published in: Journal of allergy and clinical immunology Vol. 114; no. 1; pp. 73 - 79
• Main Authors: Parameswaran, Krishnan, Liang, Hong, Fanat, Adrian, Watson, Richard, Snider, Denis P, M. O'Byrne, Paul
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.07.2004; Elsevier; Elsevier Limited
• Subjects: Adult; allergen inhalation; Allergens - adverse effects; Allergens - immunology; Allergies; asthma; Asthma - drug therapy; Asthma - immunology; Biological and medical sciences; Bronchial Hyperreactivity - drug therapy; Bronchial Hyperreactivity - immunology; Cell Count; Chemokines; Chemotactic Factors - immunology; Chromones - pharmacology; Chromones - therapeutic use; Cross-Over Studies; Cysteinyl leukotrienes; dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Double-Blind Method; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immune system; Immunopathology; Leukotriene Antagonists - pharmacology; Leukotriene Antagonists - therapeutic use; Lymphatic system; Medical sciences; Membrane Proteins - drug effects; Membrane Proteins - immunology; Middle Aged; Migration; pranlukast; Receptors, Leukotriene - drug effects; Receptors, Leukotriene - immunology; Sputum - chemistry; Sputum - immunology; allergen inhalation; Cysteinyl leukotrienes; dendritic cells; MIP; pranlukast; EAR; asthma; LAR; CysLT1; Lung disease; Allergy; Dendritic cell; Immunopathology; dendritic cells. allergen inhalation; Respiratory disease; Arachidonic acid derivatives; Antiasthma agent; Antiallergic; Asthma; Inhalation; Leukotriene; Immunology; Antigen presenting cell; Pranlukast; Eicosanoid; Benzamide derivatives; Bronchus disease; Obstructive pulmonary disease; Allergen
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2004.03.054

Dendritic cells are important antigen-presenting cells. After an allergen inhalation, their numbers rapidly decrease in circulation and increase in the airway mucosa. To investigate whether allergen-induced changes in the number of circulating dendritic cells are mediated by cysteinyl leukotrienes. 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. 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 1α and 3α 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 Δ from baseline, +4.4%) compared with placebo (mean Δ, −8.4; P < .05), but not CD123+ cells. 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.