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Role for cysteinyl leukotrienes in allergen-induced change in circulating dendritic cell number in asthma.
J Allergy Clin Immunol. 2004 Jul; 114(1):73-9.JA

Abstract

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+Show Affiliations

Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Department of Medicine, McMaster University, Hamilton, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15241347

Citation

Parameswaran, Krishnan, et al. "Role for Cysteinyl Leukotrienes in Allergen-induced Change in Circulating Dendritic Cell Number in Asthma." The Journal of Allergy and Clinical Immunology, vol. 114, no. 1, 2004, pp. 73-9.
Parameswaran K, Liang H, Fanat A, et al. Role for cysteinyl leukotrienes in allergen-induced change in circulating dendritic cell number in asthma. J Allergy Clin Immunol. 2004;114(1):73-9.
Parameswaran, K., Liang, H., Fanat, A., Watson, R., Snider, D. P., & O'Byrne, P. M. (2004). Role for cysteinyl leukotrienes in allergen-induced change in circulating dendritic cell number in asthma. The Journal of Allergy and Clinical Immunology, 114(1), 73-9.
Parameswaran K, et al. Role for Cysteinyl Leukotrienes in Allergen-induced Change in Circulating Dendritic Cell Number in Asthma. J Allergy Clin Immunol. 2004;114(1):73-9. PubMed PMID: 15241347.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role for cysteinyl leukotrienes in allergen-induced change in circulating dendritic cell number in asthma. AU - Parameswaran,Krishnan, AU - Liang,Hong, AU - Fanat,Adrian, AU - Watson,Richard, AU - Snider,Denis P, AU - O'Byrne,Paul M, PY - 2004/7/9/pubmed PY - 2004/9/29/medline PY - 2004/7/9/entrez SP - 73 EP - 9 JF - The Journal of allergy and clinical immunology JO - J Allergy Clin Immunol VL - 114 IS - 1 N2 - 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. SN - 0091-6749 UR - https://www.unboundmedicine.com/medline/citation/15241347/Role_for_cysteinyl_leukotrienes_in_allergen_induced_change_in_circulating_dendritic_cell_number_in_asthma_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&amp;PAGE=linkout&amp;SEARCH=15241347.ui DB - PRIME DP - Unbound Medicine ER -