Document Detail


Role for cysteinyl leukotrienes in allergen-induced change in circulating dendritic cell number in asthma.
MedLine Citation:
PMID:  15241347     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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. 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.
Authors:
Krishnan Parameswaran; Hong Liang; Adrian Fanat; Richard Watson; Denis P Snider; Paul M O'Byrne
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of allergy and clinical immunology     Volume:  114     ISSN:  0091-6749     ISO Abbreviation:  J. Allergy Clin. Immunol.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-07-08     Completed Date:  2004-09-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1275002     Medline TA:  J Allergy Clin Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  73-9     Citation Subset:  AIM; IM    
Copyright Information:
Copyright 2004 American Academy of Allergy, Asthma and Immunology
Affiliation:
Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Department of Medicine, McMaster University, Hamilton, Canada.
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MeSH Terms
Descriptor/Qualifier:
Adult
Allergens / adverse effects,  immunology
Asthma / drug therapy,  immunology*
Bronchial Hyperreactivity / drug therapy,  immunology
Cell Count
Chemotactic Factors / immunology
Chromones / pharmacology*,  therapeutic use
Cross-Over Studies
Dendritic Cells / drug effects*,  immunology
Double-Blind Method
Humans
Leukotriene Antagonists / pharmacology*,  therapeutic use
Membrane Proteins / drug effects,  immunology*
Middle Aged
Receptors, Leukotriene / drug effects,  immunology*
Sputum / chemistry,  immunology
Chemical
Reg. No./Substance:
0/Allergens; 0/Chemotactic Factors; 0/Chromones; 0/Leukotriene Antagonists; 0/Membrane Proteins; 0/Receptors, Leukotriene; 0/leukotriene D4 receptor; 0/pranlukast

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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