Reduced expression of the prostaglandin E₂ receptor E-prostanoid 2 on bronchial mucosal leukocytes in patients with aspirin-sensitive asthma

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• 作者：Chris J. Corrigan ; MD ; PhD ; Rahilya L. Napoli ; MS ; Qiu Meng ; MD ; Cailong Fang ; MD ; PhD ; Huifen Wu ; MD ; Keri Tochiki ; MSc ; Victoria Reay ; MD ; Tak H. Lee ; MD ; DSc ; Sun Ying ; MD ; PhD ; ^{ying.sun@kcl.ac.uk}
• 关键词：Aspirin ; prostaglandin E2 ; E-prostanoid receptor ; asthma
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2012
• 期刊代码：158_00916749
• 类别：med
• 出版时间：June, 2012
• 卷：129
• 期：6
• 页码：1636-1646
• 文件大小：1280 K

摘要

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Background

Prostaglandin E₂ (PGE₂) is thought to play a role in the pathogenesis of aspirin-sensitive asthma (ASA).

Objective

We sought to extend our previous observations implicating impaired inflammatory cell responsiveness to PGE₂ as a pathogenetic mechanism in patients with aspirin-sensitive rhinosinusitis to the bronchial mucosa in patients with ASA.

Methods

Immunohistochemistry was used to enumerate inflammatory cells and their expression of cysteinyl leukotriene receptors 1 and 2 (CysLT₁ and CysLT₂) and the PGE₂ receptors E-prostanoid 1 to 4 (EP₁-EP₄) in bronchial biopsy specimens from patients with ASA, patients with aspirin-tolerant asthma, and control subjects (n聽= 15 in each group). Concentrations of PGE₂ in bronchoalveolar lavage fluid were measured by using ELISA. The effects of PGE₂ and EP receptor agonists on CD3/CD28-stimulated cytokine production by PBMCs were measured by using ELISA. Airways responsiveness to LTD₄ in聽vivo was measured in asthmatic patients by means of bronchial challenge.

Results

Compared with patients with aspirin-tolerant asthma, patients with ASA had increased bronchial mucosal neutrophil and eosinophil numbers but reduced percentages of T cells, macrophages, mast cells, and neutrophils expressing EP₂. Both groups showed increased bronchial sensitivity to inhaled LTD₄, but this did not correlate with mucosal expression of CysLT₁ or CysLT₂. Bronchoalveolar lavage fluid PGE₂ concentrations were comparable in all groups. In聽vitro PGE₂ inhibited cytokine production by PBMCs through EP₂ but not other PGE₂ receptors.

Conclusion

Our data are consistent with the hypothesis that impaired inhibition of inflammatory leukocytes by PGE₂ acting through the EP₂ receptor has a role in the pathogenesis of ASA.