Research upregulation of CD23 (FcεRII) expression in human airway smooth muscle cells (huASMC) in response to IL-4, GM-CSF, and IL-4/GM-CSF

被引：12

作者：

Belleau J.T. ^{[1
]}

Gandhi R.K. ^{[1
]}

McPherson H.M. ^{[1
]}

Lew D.B. ^{[1
]}

机构：

[1] Department of Pediatrics, Children's Foundation Research Center at the Le Bonheur Children's Medical Center, University of Tennessee Health Science Center, Memphis, TN 38103

来源：

Clinical and Molecular Allergy | / 3卷 / 1期

关键词：

CD23 Expression; Tryptase; Airway Smooth Muscle Cell; Human Airway Smooth Muscle Cell; Membrane Ruffling;

D O I：

10.1186/1476-7961-3-6

中图分类号：

学科分类号：

摘要：

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. The percentage of cells with increased fluorescence intensity above the control was 25.1 ± 4.2% (IL-4), 15.6 ± 2.75% (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-A, 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-4Rα and a low level expression of IL-2Rγc in huASMC. Stimulation with IL-4 resulted in the phosphorylation of STAT-6 and an increase in the expression of the IL-2Rγc. Conclusion: CD23 on huASMC is upregulated by IL-a, GM-.CSF, and. IL-4/GM-CSF. The expression of CD23 is accompanied by an increase in cell volume and an increase in protein content per cell, 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 huASMC and may provide an avenue for new therapeutic options in asthma targeting ASMC. © 2005 Belleau et al; licensee BioMed Central Ltd.

引用

页数：12

共 35 条

[1]

Vignola A.M., Effects of inhaled corticosteroids, leukotriene receptor antagonists, or both, plus long-acting beta2-agonists on asthma pathophysiology: A review of evidence, Drugs, 63, pp. 35-51, (2003)

[2]

Benayoun L., Druihe A., Dombret M.-C., Aubier M., Pretolani M., Airway structural alterations selectively associated with severe asthma, Am. J. Respir. Crit. Care Med., 167, pp. 1360-1368, (2003)

[3]

Woodruff P.G., Dolganov G.M., Ferrando R.E., Donnelly S., Hays S.R., Solberg O.D., Carter R., Wong H.H., Cadbury P.S., Fahy J.V., Hyperplasia of smooth muscle in mild to moderate asthma without changes in cell size or gene expression, Am. J. Respir. Crit. Care Med., 169, pp. 1001-1006, (2004)

[4]

Hirst S.J., Regulation of airway smooth muscle cell immunomodulatory function: Role in asthma, Respir. Physiol. Neurobiol., 137, pp. 309-326, (2003)

[5]

Busse W., Banks-Schlegel S., Wenzel S., Pathophysiology of severe asthma, Nihlbi workshop summary, J. Allerg. Clin. Immunol., 106, pp. 1033-1042, (2000)

[6]

Hakonarson H., Grunstein M., Autocrine regulation of airway smooth muscle responsiveness, Respir. Physiol. & Neurobiol., 137, pp. 263-276, (2003)

[7]

Madison M., Migration of airway smooth muscle cells, Am. J. Respir. Cell. Mol. Biol., 29, pp. 8-11, (2003)

[8]

Schmidt D., Rabe K., Immune mechanisms of smooth muscle hyperreactivity in asthma, J. Allerg. Clin. Immunol., 105, pp. 673-683, (2000)

[9]

Broide D., Novel therapies in allergic disease: Molecular and cellular mechanisms of allergic disease, J. Allerg. Clin. Immunol., 108, SUPPL., pp. 65-71, (2001)

[10]

Matz J., Williams J., Rosenwasser L., Borish L., Granulocyte-macrophage colony-stimulating factor stimulates macrophages to respond to IgE via the low affinity IgE receptor (CD23), J. Allerg. Clin. Immunol., 93, pp. 650-657, (1994)

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