Nasal mucosal expression of the leukotriene and prostanoid pathways in seasonal and perennial allergic rhinitis.
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.
Westergren
V S
VS
Division of Infection, Inflammation and Repair, University of Southampton School of Medicine, Southampton, UK.
Wilson
S J
SJ
Penrose
J F
JF
Howarth
P H
PH
Sampson
A P
AP
D058927:5-Lipoxygenase-Activating Proteins; D000293:Adolescent; D000328:Adult; D000368:Aged; D001094:Arachidonate 5-Lipoxygenase / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000096:biosynthesis / Q000276:immunology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis / Q000276:immunology; D017572:Leukotriene A4 / Q000096:biosynthesis / Q000276:immunology; D017997:Leukotriene C4 / Q000096:biosynthesis / Q000276:immunology; D015289:Leukotrienes / Q000096:biosynthesis / Q000276:immunology*; D054834:Lipocalins / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology* / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis / Q000276:immunology*; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D055815:Young Adult
D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D002352:Carrier Proteins; D017572:Leukotriene A4; D015289:Leukotrienes; D054834:Lipocalins; D008565:Membrane Proteins; D011453:Prostaglandins; D017997:Leukotriene C4; D001094:Arachidonate 5-Lipoxygenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase