title: Aspirin-sensitive rhinosinusitis is associated with reduced E-prostanoid 2 receptor expression on nasal mucosal inflammatory cells.
abstract: BACKGROUND
  Impaired braking of inflammatory cell cysteinyl leukotriene production by prostaglandin (PG) E(2) has been implicated in the pathogenesis of aspirin exacerbated airways disease, but the mechanism is obscure. PGE(2) acts via G-protein-coupled receptors, E-prostanoid (EP)(1-4,) but there is little information on the expression of PGE(2) receptors in this condition.
  
  
  OBJECTIVE
  To address the hypothesis that expression of 1 or more EP receptors on nasal mucosal inflammatory cells is deficient in patients with aspirin-sensitive compared with nonaspirin-sensitive polypoid rhinosinusitis.
  
  
  METHODS
  By using specific antibodies, immunohistochemistry, and image analysis, we measured the expression of EP(1-4) in nasal biopsies from patients with aspirin-sensitive (n = 12) and nonaspirin-sensitive (n = 10) polypoid rhinosinusitis and normal controls (n = 9). Double-staining was used to phenotype inflammatory leukocytes expressing EP(1-4).
  
  
  RESULTS
  Global mucosal expression of EP(1) and EP(2), but not EP(3) or EP(4), immunoreactivity was significantly elevated in aspirin-sensitive and nonaspirin-sensitive rhinosinusitis compared with controls (P < .03). This was attributable principally to elevated expression on tubulin(+) epithelial cells and Mucin 5 subtypes A and B (Muc-5AC(+)) goblet cells. In contrast, the percentages of neutrophils, mast cells, eosinophils, and T cells expressing EP(2), but not EP(1), EP(3), or EP(4), were significantly reduced (P < or = .04) in the aspirin-sensitive compared with nonaspirin-sensitive patients.
  
  
  CONCLUSIONS
  The data suggest a possible role for PGE(2) in mediating epithelial repair in rhinitis and asthma. Because PGE(2) exerts a range of inhibitory actions on inflammatory leukocytes via the EP(2) receptor, its reduced expression in aspirin-sensitive rhinosinusitis may be partly responsible for the increased inflammatory infiltrate and production of cysteinyl leukotrienes that characterize aspirin-sensitive disease.
authors.affiliation: King's College London, MRC and Asthma UK Centre, Department of Asthma, Allergy and Respiratory Science, UK. ying.sun@kcl.ac.uk
authors.forename: Sun
authors.initials: S
authors.lastname: Ying
authors.forename: Qiu
authors.initials: Q
authors.lastname: Meng
authors.forename: Glenis
authors.initials: G
authors.lastname: Scadding
authors.forename: Abhi
authors.initials: A
authors.lastname: Parikh
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Corrigan
authors.forename: Tak H
authors.initials: TH
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D001706:Biopsy; D002908:Chronic Disease; D004342:Drug Hypersensitivity / Q000209:etiology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology; D007962:Leukocytes / Q000378:metabolism*; D008875:Middle Aged; D009297:Nasal Mucosa / Q000166:cytology / Q000276:immunology*; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D012220:Rhinitis / Q000139:chemically induced*; D012852:Sinusitis / Q000139:chemically induced*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018078:Receptors, Prostaglandin E; D001241:Aspirin