Reduced expression of the prostaglandin E2 receptor E-prostanoid 2 on bronchial mucosal leukocytes in patients with aspirin-sensitive asthma
| Autor: | Cailong Fang, Keri Tochiki, Qiu Meng, Sun Ying, Victoria Reay, Christopher Corrigan, Tak H. Lee, Huifen Wu, Rahilya L Napoli |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Prostaglandin E2 receptor medicine.medical_treatment Immunology Bronchi Respiratory Mucosa Young Adult chemistry.chemical_compound Leukocytes medicine Humans Immunology and Allergy Prostaglandin E2 Receptors Leukotriene Leukotriene E4 medicine.diagnostic_test biology business.industry Middle Aged Receptors Prostaglandin E EP2 Subtype Eosinophil medicine.anatomical_structure Bronchoalveolar lavage Cytokine chemistry Leukocytes Mononuclear Major basic protein biology.protein Cytokines Asthma Aspirin-Induced Female lipids (amino acids peptides and proteins) business Bronchoalveolar Lavage Fluid Prostaglandin E medicine.drug |
| Zdroj: | Journal of Allergy and Clinical Immunology. 129:1636-1646 |
| ISSN: | 0091-6749 |
| DOI: | 10.1016/j.jaci.2012.02.007 |
| Popis: | Background Prostaglandin E 2 (PGE 2 ) 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 PGE 2 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 (CysLT 1 and CysLT 2 ) and the PGE 2 receptors E-prostanoid 1 to 4 (EP 1 -EP 4 ) in bronchial biopsy specimens from patients with ASA, patients with aspirin-tolerant asthma, and control subjects (n = 15 in each group). Concentrations of PGE 2 in bronchoalveolar lavage fluid were measured by using ELISA. The effects of PGE 2 and EP receptor agonists on CD3/CD28-stimulated cytokine production by PBMCs were measured by using ELISA. Airways responsiveness to LTD 4 in 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 EP 2 . Both groups showed increased bronchial sensitivity to inhaled LTD 4 , but this did not correlate with mucosal expression of CysLT 1 or CysLT 2 . Bronchoalveolar lavage fluid PGE 2 concentrations were comparable in all groups. In vitro PGE 2 inhibited cytokine production by PBMCs through EP 2 but not other PGE 2 receptors. Conclusion Our data are consistent with the hypothesis that impaired inhibition of inflammatory leukocytes by PGE 2 acting through the EP 2 receptor has a role in the pathogenesis of ASA. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect