Cysteinyl leukotriene expression in chronic hyperplastic sinusitis-nasal polyposis: Importance to eosinophilia and asthma

John W. Steinke, Dewayne Bradley, Pablo Arango, Charles D. Crouse, Henry Frierson, Stilianos E Kountakis, Monica Kraft, Larry Borish

Research output: Contribution to journalArticle

126 Scopus citations

Abstract

Background: Chronic hyperplastic eosinophilic sinusitis (CHS) results from the unregulated proliferation of eosinophils, TH2-like lymphocytes, goblet cells, mast cells, and fibroblasts and is present in most patients with asthma. The frequent coexpression of these disorders and their shared pathophysiology suggests that these are similar disorders affecting the upper and lower airways. Objective: We evaluated the expression of cysteinyl leukotrienes (CysLTs) in sinus tissue from subjects with CHS compared with that seen in healthy sinus tissue. Methods: Nasal polyp and sinus tissue was evaluated from 58 individuals undergoing elective functional endoscopic sinus surgery. The diagnosis of CHS was demonstrated through the presence of eosinophilia and activated (EG2+) eosinophils, as determined by means of tissue immunohistochemistry. Data were compared with those from both nasal polyp tissue without eosinophilic inflammation and healthy control sinus tissue obtained from the sinus ostiomeatal complex at the time of surgery for unrelated disorders. CysLTs were quantified by means of ELISA in lipid-extracted tissue. Activation of the metabolic pathway leading to CysLT synthesis was demonstrated by ribonuclease protection. Subjects were genotyped for leukotriene C4 (LTC4) synthase C-to-A promoter polymorphism. Results: CysLT concentrations were significantly higher in tissue obtained from subjects with CHS (776.7 ± 201.9 pg/g tissue) compared with that seen in healthy sinus tissue (355.7 ± 101.6 pg/g tissue, P < .03). CysLT concentrations within noneosinophilic nasal polyps (328.0 ± 116.4 pg/g tissue) were similar to those in control tissue. The presence of CysLTs in CHS was associated with increased expression of LTC4 synthase mRNA. The C-to-A promoter polymorphism was associated with trends toward the increased presence of CHS and CysLTs. Conclusions: CHS is characterized by the increased presence of CysLTs when compared with concentrations seen in tissue from patients with chronic inflammatory sinusitis or healthy sinus tissue. These studies support the use of LT modifiers as anti-inflammatory agents that might have clinical benefit in patients with these disorders.

Original languageEnglish (US)
Pages (from-to)342-349
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume111
Issue number2
DOIs
Publication statusPublished - Feb 1 2003
Externally publishedYes

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Keywords

  • Asthma
  • Chronic hyperplastic sinusitis
  • Cysteinyl leukotrienes
  • Eosinophils
  • Leukotriene C4 synthase
  • Nasal polyps
  • Polymorphisms

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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