title: Reduced expression of the prostaglandin E2 receptor E-prostanoid 2 on bronchial mucosal leukocytes in patients with aspirin-sensitive asthma.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Asthma, Allergy & Lung Biology, King's College London, MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Corrigan
authors.forename: Rahilya L
authors.initials: RL
authors.lastname: Napoli
authors.forename: Qiu
authors.initials: Q
authors.lastname: Meng
authors.forename: Cailong
authors.initials: C
authors.lastname: Fang
authors.forename: Huifen
authors.initials: H
authors.lastname: Wu
authors.forename: Keri
authors.initials: K
authors.lastname: Tochiki
authors.forename: Victoria
authors.initials: V
authors.lastname: Reay
authors.forename: Tak H
authors.initials: TH
authors.lastname: Lee
authors.forename: Sun
authors.initials: S
authors.lastname: Ying
mesh_terms: D000328:Adult; D055963:Asthma, Aspirin-Induced / Q000276:immunology / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018077:Receptors, Leukotriene / Q000378:metabolism; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000819:agonists / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016207:Cytokines; D018077:Receptors, Leukotriene; D058307:Receptors, Prostaglandin E, EP2 Subtype; C412375:cysteinyl leukotriene receptor 2; C083169:leukotriene D4 receptor