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

Nasal mucosal expression of the leukotriene and prostanoid pathways in seasonal and perennial allergic rhinitis
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.
0954-7894
820-828
Westergren, V.S.
5cee6a6b-5629-4d82-9063-c8020479225d
Wilson, S.J.
21c6875d-6870-441b-ae7a-603562a646b8
Penrose, J.F.
3a1b8c7d-7ea8-4736-80e2-8199e269728e
Howarth, P.H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Sampson, A.P.
4ca76f6f-ff35-425d-a7e7-c2bd2ea2df60
Westergren, V.S.
5cee6a6b-5629-4d82-9063-c8020479225d
Wilson, S.J.
21c6875d-6870-441b-ae7a-603562a646b8
Penrose, J.F.
3a1b8c7d-7ea8-4736-80e2-8199e269728e
Howarth, P.H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Sampson, A.P.
4ca76f6f-ff35-425d-a7e7-c2bd2ea2df60

Westergren, V.S., Wilson, S.J., Penrose, J.F., Howarth, P.H. and Sampson, A.P. (2009) Nasal mucosal expression of the leukotriene and prostanoid pathways in seasonal and perennial allergic rhinitis. Clinical & Experimental Allergy, 39 (6), 820-828. (doi:10.1111/j.1365-2222.2009.03223.x).

Record type: Article

Abstract

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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Published date: June 2009
Organisations: Infection Inflammation & Immunity

Identifiers

Local EPrints ID: 72805
URI: http://eprints.soton.ac.uk/id/eprint/72805
ISSN: 0954-7894
PURE UUID: 53bbb094-e75b-447a-8924-f78adb98d949
ORCID for S.J. Wilson: ORCID iD orcid.org/0000-0003-1305-8271
ORCID for A.P. Sampson: ORCID iD orcid.org/0009-0008-9653-8935

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Date deposited: 23 Feb 2010
Last modified: 14 Mar 2024 02:39

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Contributors

Author: V.S. Westergren
Author: S.J. Wilson ORCID iD
Author: J.F. Penrose
Author: P.H. Howarth
Author: A.P. Sampson ORCID iD

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