Upregulation of CD23 (FceRII) Expression in Human Airway Smooth Muscle Cells (huASMC) in Response to IL-4, GM-CSF, and IL-4/GM-CSF

Background: Airway smooth muscle cells play a key role in remodeling that contributes to airway hyperreactivity.

Category: Clinical-and-Molecular-Allergy

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Background: Airway smooth muscle cells play a key role in remodeling that contributes to airway hyperreactivity. Airway smooth muscle remodeling includes hypertrophy and hyperplasia. It has been previously shown that the expression of CD23 on ASMC in rabbits can be induced by the IgE component of the atopic serum. We examined if other components of atopic serum are capable of inducing CD23 expression independent of IgE. Methods: Serum starved huASMC were stimulated with either IL-4, GM-CSF, IL-13, IL-5, PGD2, LTD4, tryptase or a combination of IL-4, IL-5, IL-13 each with GM-CSF for a period of 24 h. CD23 expression was analyzed by flow cytometry, western blot, and indirect immunofluorescence. Results: The CD23 protein expression was upregulated in huASMC in response to IL-4, GM-CSF, and IL-4/GM-CSF with a synergistic effect of IL-4/GM-CSF when compared to vehicle controls. The percentage of cells with increased fluorescence intensity above the control was 25.1 + 4.2% (IL-4), 15.6 + 2.7% (GM-CSF) and 32.9 + 13.9% (IL-4/GMCSF combination)(n=3). The protein content of IL-4/GMCSF stimulated cells was significantly elevated. Expression of CD23 in response to IL-4, GM-CSF, IL-4/GM-CSF was accompanied by changes in cell morphology including depolymerization of isoactin fibers, cell spreading, and membrane ruffling. Western blot revealed abundant expression of the IL-4Ralpha and a low level expression of IL-2Rgammac in huASMC. Stimulation with IL-4 resulted in the phosphorylation of STAT-6 and an increase in the expression of the IL-2Rgammac. Conclusions: CD23 on huASMC is upregulated by IL-4, GM-CSF, and IL-4/GM-CSF. The combination of IL-4/GM-CSF has a synergistic effect and is accompanied by an increase in cell volume and an increase in protein content, suggesting hypertrophy. Upregulation of CD23 by IL-4/GM-CSF results in phenotypic changes in huASMC that could play a role in cell migration or a change in the synthetic function of the cells. Upregulation of CD23 in huASMC by IL-4 and GM-CSF can contribute to changes in the hypertrophic asthma phenotype and may provide an avenue for new therapeutic options in asthma targeting ASMC. http://www.clinicalmolecularallergy.com/content/3/1/6

Joseph T Belleau, Radha K Gandhi, Holly M McPherson and D.Betty Lew

Clinical and Molecular Allergy 2005, 3:6

2005-05-20

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