Expression of prostaglandin E₂ receptor subtypes on cells in sputum from patients with asthma and controls: Effect of allergen inhalational challenge

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• 作者：Sun Ying ; Brian J. O'Connor ; Qiu Meng ; Natalie Woodman ; Steven Greenaway ; Helen Wong ; Kirsty Mallett ; Tak H. Lee ; Chris Corrigan
• 关键词：Prostaglandin E₂ ; EP receptor ; immunocytochemistry ; asthma ; allergen challenge ; sputum
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2004
• 出版时间：December 2004
• 年：2004
• 卷：114
• 期：6
• 页码：1309-1316
• 全文大小：322 K

文摘

Background

Prostaglandin (PG) E₂ binds to 4 G-protein–coupled receptors designated EP₁ through EP₄. Although PGE₂ plays an immunomodulatory role in asthma, there is little information on the expression of PGE₂ receptors in this disease.

Objective

We hypothesized that profiles of E-prostanoid (EP) receptor expression are altered on asthmatic bronchial inflammatory cells in vivo and further altered by allergen challenge in vivo and proinflammatory mediators in vitro.

Methods

The numbers and phenotypes of EP_1-4 immunoreactive induced sputum cells from atopic asthmatics (n = 13; before and 24 hours after allergen inhalational challenge) and normal controls (n = 9; 3 after saline challenge) and EP_1-4 expression on purified blood eosinophils from both groups (n = 4 for each) before and after stimulation with LPS and/or IL-5 in vitro were measured by using single and double immunocytochemistry.

Results

Subsets of sputum cells of all phenotypes expressed all 4 EP receptors in both patients with asthma and controls. There were significantly greater numbers of macrophages expressing all 4 EP receptors and increased percentages of macrophages expressing EP₂ and EP₄ in patients with asthma compared with controls. Allergen bronchial challenge of patients with asthma was associated with a selective influx of eosinophils, but the percentages of these and other leukocytes expressing all 4 EP receptors were unchanged. Compared with sputum, only small percentages of peripheral blood eosinophils expressed each receptor, but this was increased by culture with exogenous IL-5 or LPS.

Conclusion

E-prostanoid receptor expression is increased on airway macrophages of patients with asthma at baseline and may be altered on eosinophils after allergen challenge in vivo in response to inflammatory stimuli.