Reduced expression of the prostaglandin E2 receptor E-prostanoid 2 on bronchial mucosal leukocytes in patients with aspirin-sensitive asthma - 31/05/12
Corresponding author: Sun Ying, MD, PhD, Division of Asthma, Allergy & Lung Biology, King’s College London, MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, 5th Floor Tower Wing, Guy’s Hospital, London SE1 9RT, United Kingdom.Abstract |
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 = 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 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 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.
Le texte complet de cet article est disponible en PDF.Key words : Aspirin, prostaglandin E2, E-prostanoid receptor, asthma
Abbreviations used : AERD, ASA, BAL, Ct, CysLT, EP, HC, LTE4, MBP, NASA, PGE2
Plan
| Supported by the Medical Research Council and Asthma UK and the Department of Health through a National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre award to Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust. |
|
| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 129 - N° 6
P. 1636-1646 - juin 2012 Retour au numéro
Article précédent
- CRACM/Orai ion channel expression and function in human lung mast cells
- Ian Ashmole, S. Mark Duffy, Mark L. Leyland, Valerie S. Morrison, Malcolm Begg, Peter Bradding
- Tolerance induction with T cell–dependent protein antigens induces regulatory sialylated IgGs
- Carolin M. Oefner, André Winkler, Constanze Hess, Alexandra K. Lorenz, Vivien Holecska, Melanie Huxdorf, Tim Schommartz, Dominique Petzold, Josephine Bitterling, Anna-Lena Schoen, Alexander D. Stoehr, Dana Vu Van, Yasemin Darcan-Nikolaisen, Véronique Blanchard, Inken Schmudde, Yves Laumonnier, Heike A. Ströver, Ahmed N. Hegazy, Susanne Eiglmeier, Carolin T. Schoen, Maria M.M. Mertes, Christoph Loddenkemper, Max Löhning, Peter König, Arnd Petersen, Elke O. Luger, Mattias Collin, Jörg Köhl, Andreas Hutloff, Eckard Hamelmann, Markus Berger, Hedda Wardemann, Marc Ehlers
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?