Document Detail


CC chemokine receptor 4 (CCR4) in human allergen-induced late nasal responses.
MedLine Citation:
PMID:  20148806     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: CC Chemokine receptor 4 (CCR4) is preferentially expressed on Th2 lymphocytes. CCR4-mediated inflammation may be important in the pathology of allergic rhinitis. Disruption of CCR4 - ligand interaction may abrogate allergen-induced inflammation.
METHODS: Sixteen allergic rhinitics and six nonatopic individuals underwent both allergen and control (diluent) nasal challenges. Symptom scores and peak nasal inspiratory flow were recorded. Nasal biopsies were taken at 8 h post challenge. Sections were immunostained and examined by light or dual immunofluorescence microscopy for eosinophils, T-lymphocytes, CCR4(+)CD3(+) and CXCR3(+)CD3(+) cells and examined by in situ hybridization for CCR4, IL-4 and IFN-gamma mRNA(+) cells. Peripheral blood mononuclear cells were obtained from peripheral blood of nine normal donors and the CCR4(+)CD4(+) cells assessed for actin polymerization in response to the CCR4 ligand macrophage-derived chemokine (MDC/CCL22) and the influence of a CCR4 antagonist tested.
RESULTS: Allergic rhinitics had increased early and late phase symptoms after allergen challenge compared to diluent; nonatopics did not respond to either challenge. Eosinophils, but not total numbers of CD3(+) T cells, were increased in rhinitics following allergen challenge. In rhinitics, there was an increase in CCR4(+)CD3(+) protein-positive cells relative to CXCR3(+)CD3(+) cells; CCR4 mRNA+ cells were increased and IL-4 increased to a greater extent than IFN-gamma. CCR4(+)CD4(+) T cells responded to MDC in vitro, and this response was inhibited by the selective CCR4 antagonist.
CONCLUSION: Lymphocyte CCR4 expression is closely associated with induction of human allergen-induced late nasal responses. Blocking CCR4-ligand interaction may provide a novel therapeutic approach in allergic disease.
Authors:
G Banfield; H Watanabe; G Scadding; M R Jacobson; S J Till; D A Hall; D S Robinson; C M Lloyd; K T Nouri-Aria; S R Durham
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2010-02-10
Journal Detail:
Title:  Allergy     Volume:  65     ISSN:  1398-9995     ISO Abbreviation:  Allergy     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-16     Completed Date:  2011-01-10     Revised Date:  2012-09-20    
Medline Journal Info:
Nlm Unique ID:  7804028     Medline TA:  Allergy     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  1126-33     Citation Subset:  IM    
Affiliation:
Department of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, London, UK.
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MeSH Terms
Descriptor/Qualifier:
Administration, Intranasal
Adult
Allergens / administration & dosage,  immunology*
Biopsy
Female
Humans
Hypersensitivity, Immediate / immunology*,  physiopathology
Inflammation / immunology,  physiopathology
Male
Nasal Mucosa / immunology,  metabolism
Receptors, CCR4 / genetics,  metabolism*
Rhinitis, Allergic, Perennial / immunology*,  physiopathology
Rhinitis, Allergic, Seasonal / immunology*,  physiopathology
Th2 Cells / immunology,  metabolism*
Time Factors
Grant Support
ID/Acronym/Agency:
057704//Wellcome Trust; //Medical Research Council
Chemical
Reg. No./Substance:
0/Allergens; 0/Receptors, CCR4
Comments/Corrections

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