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Nasal mucosal expression of the leukotriene and prostanoid pathways in seasonal and perennial allergic rhinitis.

Authors: Westergren, VS  Wilson, SJ  Penrose, JF  Howarth, PH  Sampson, AP 
Citation: Westergren VS, etal., Clin Exp Allergy. 2009 Jun;39(6):820-8. Epub 2009 Apr 2.
Pubmed: (View Article at PubMed) PMID:19364335
DOI: Full-text: DOI:10.1111/j.1365-2222.2009.03223.x

BACKGROUND: Leukotrienes (LTs) and prostanoids are potent pro-inflammatory and vasoactive lipid mediators implicated in airway disease, but their cellular sources in the nasal airway in naturally occurring allergic rhinitis (AR) are unclear. OBJECTIVE: To quantify cellular expression of enzymes of the 5-lipoxygenase (5-LO) and cyclooxygenase (COX) pathways by immunohistochemistry in nasal biopsies from patients with symptomatic perennial AR (PAR, n = 13) and seasonal AR (SAR, n = 14) and from normal subjects (n = 12). METHODS: Enzymes of the 5-LO pathway (5-LO, FLAP, LT A4 hydrolase, LTC4 synthase) and the COX pathway (COX-1, COX-2, prostaglandin D2 synthase) were immunostained in glycol methacrylate resin-embedded inferior turbinate biopsy specimens, quantified in the lamina propria and epithelium, and co-localized to leucocyte markers by camera lucida. RESULTS: In the lamina propria of PAR biopsies, median counts of cells expressing FLAP were fourfold higher than in normal biopsies (Mann-Whitney, P = 0.014), and also tended to be higher than in SAR biopsies (P = 0.06), which were not different from normal. PAR biopsies showed threefold more cells immunostaining for LTC4 synthase compared with SAR biopsies (P = 0.011) but this was not significant compared with normal biopsies (P = 0.2). These changes were associated with ninefold more eosinophils (P = 0.0005) with no differences in other leucocytes. There were no significant differences in the lamina propria in immunostaining for 5-LO, LTA4 hydrolase, COX-1, COX-2 or PGD2 synthase. Within the epithelium, increased expression of COX-1 was evident in PAR biopsies (P = 0.014) and SAR biopsies (P = 0.037), associated with more intra-epithelial mast cells in both rhinitic groups (P < 0.02). CONCLUSIONS: In the nasal biopsies of PAR subjects, increased expression of regulatory enzymes of the cysteinyl-LT biosynthetic pathway was associated with lamina propria infiltration by eosinophils. Seasonal rhinitis biopsies shared only some of these changes, consistent with transient disease. Increased intra-epithelial mast cells and epithelial COX-1 expression in both rhinitic groups may generate modulatory prostanoids.

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CRRD Object Information
CRRD ID: 5147461
Created: 2011-08-05
Species: All species
Last Modified: 2011-08-05
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.