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Immunoglobulin E-dependent regulation of the CCR3 chemokine receptor by interferon-gamma in atopic asthmatics.

AbstractBACKGROUND:
The chemokine receptor CCR3 mediates the migration of cells that play an important role in the pathogenesis of asthma to inflammatory foci. Interferon (IFN)-gamma is known to downregulate the expression of some chemokine receptors. Therefore, we decided to analyze the regulation of CCR3 by IFN-gamma in asthmatics and to characterize the dependence of this process on immunoglobulin E (IgE) levels.
METHODS:
Atopic asthmatics were treated with IFN-gamma or placebo, and the IgE concentration in the blood was measured using an ultra-micro-ELISA for total IgE. Mononuclear cells from patients and controls were isolated by Ficoll-Hypaque gradient and incubated in the absence or presence of IFN-gamma for different periods of time. After incubation, the cells were washed and lysed for RT-PCR analysis, which was performed using a Perkin-Elmer kit.
RESULTS:
IFN-gamma treatment apparently improved the evaluated clinical variables; however, the differences were not significant compared to the placebo group. We found that IFN-gamma downregulated CCR3 mRNA expression ex vivo and in vivo in those patients with IgE levels higher than 500 IU/ml, whereas IFN-gamma upregulated CCR3 mRNA expression in patients with IgE levels lower than 500 IU/ml. Correspondence between ex vivo and in vivo results was observed using this approach. There was found to be a direct correlation between total serum IgE and CCR3 mRNA expression.
CONCLUSIONS:
In those asthmatic patients with high levels of IgE, who are thus susceptible to downregulation of CCR3 by IFN-gamma, a significant therapeutic effect with systemic IFN-gamma might be expected.
AuthorsYanelda García-Vega, Judith Rodríguez-Perez, Cimara Bermúdez-Badell, Elizabeth Blanco-Garcés, Carmen Valenzuela-Silva, Pedro López-Saura, Iraldo Bello-Rivero
JournalInternational archives of allergy and immunology (Int Arch Allergy Immunol) Vol. 148 Issue 3 Pg. 219-27 ( 2009) ISSN: 1423-0097 [Electronic] Switzerland
PMID18849613 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Copyright(c) 2008 S. Karger AG, Basel.
Chemical References
  • CCR3 protein, human
  • Receptors, CCR3
  • Immunoglobulin E
  • Interferon-gamma
Topics
  • Adult
  • Asthma (blood, drug therapy, genetics)
  • Cells, Cultured
  • Double-Blind Method
  • Eosinophils (cytology, drug effects, metabolism)
  • Female
  • Gene Expression Regulation (drug effects)
  • Humans
  • Immunoglobulin E (blood)
  • Interferon-gamma (pharmacology, therapeutic use)
  • Leukocyte Count
  • Leukocytes, Mononuclear (cytology, drug effects, metabolism)
  • Male
  • Middle Aged
  • Neutrophils (cytology, drug effects, metabolism)
  • Receptors, CCR3 (genetics)
  • Treatment Outcome
  • Young Adult

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