Immunoglobulin E-dependent regulation of the CCR3 chemokine receptor by interferon-gamma in atopic asthmatics.
BACKGROUND
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.
Centro de Investigaciones Biológicas, Clinical Trials Division, La Habana, Cuba.
Yanelda
Y
García-Vega
Judith
J
Rodríguez-Perez
Cimara
C
Bermúdez-Badell
Elizabeth
E
Blanco-Garcés
Carmen
C
Valenzuela-Silva
Pedro
P
López-Saura
Iraldo
I
Bello-Rivero
D000328:Adult; D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D002478:Cells, Cultured; D004311:Double-Blind Method; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007371:Interferon-gamma / Q000494:pharmacology* / Q000627:therapeutic use; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D054397:Receptors, CCR3 / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
C515350:CCR3 protein, human; D054397:Receptors, CCR3; D007073:Immunoglobulin E; D007371:Interferon-gamma