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Leukotriene and prostanoid pathway enzymes in bronchial biopsies of seasonal allergic asthmatics

Leukotriene and prostanoid pathway enzymes in bronchial biopsies of seasonal allergic asthmatics
Leukotriene and prostanoid pathway enzymes in bronchial biopsies of seasonal allergic asthmatics
Cysteinyl-leukotrienes and prostaglandin D2 generated by the 5-lipoxygenase (5-LO) and cyclooxygenase (COX) pathways, respectively, cause bronchoconstriction, leukocyte recruitment, and bronchial hyperresponsiveness in asthma. We characterized the cellular expression of 5-LO and COX enzymes using immunohistochemistry on bronchial biopsies from 12 allergic asthmatic patients before and during seasonal exposure to birch pollen.

Bronchial responsiveness (p = 0.004) and symptoms (p < 0.005) increased and peak expiratory flow (PEF; p 0.02) decreased in the pollen season. In-season biopsies had 2-fold more cells immunostaining for 5-LO (p = 0.02), 5-LO-activating protein (FLAP; p = 0.04), and leukotriene (LT)A4 hydrolase (p = 0.05), and 4-fold more for the terminal enzyme for cysteinyl-leukotriene synthesis, LTC4 synthase (p = 0.02). Immunostaining for COX-1, COX-2, and PGD2 synthase was unchanged.

Increased staining for LTC4 synthase was due to increased eosinophils (p = 0.035) and an increased proportion of eosinophils expressing the enzyme (p = 0.047). Macrophages also increased (p = 0.019), but mast cells and T-lymphocyte subsets were unchanged. Inverse correlations between PEF and 5-LO+ cell counts link increased expression of 5-LO pathway enzymes in eosinophils and macrophages within the bronchial mucosa to deterioration of lung function during seasonal allergen exposure.




1073-449X
2051-2056
Seymour, Michelle L.
a9e098fb-2371-4d47-beca-d76f877d882e
Rak, Sabina
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Aberg, Daniel
c2f80251-1e1b-420b-b4d1-a9823d88df1a
Riise, Gert
46661b69-b7d6-46fe-b8a1-f3c477029753
Penrose, John F.
a1d34fbc-ff46-49bd-a184-ba20a900239b
Kanaoka, Yoshihide
e972a977-d2b8-4078-b01a-ff6d6423ddcf
Austen, K. Frank
59cdb2b7-ff11-42a0-93db-44f643c065e1
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Sampson, Anthony P.
4ca76f6f-ff35-425d-a7e7-c2bd2ea2df60
Seymour, Michelle L.
a9e098fb-2371-4d47-beca-d76f877d882e
Rak, Sabina
3bc22489-7d42-4eea-9294-d236c10afc7e
Aberg, Daniel
c2f80251-1e1b-420b-b4d1-a9823d88df1a
Riise, Gert
46661b69-b7d6-46fe-b8a1-f3c477029753
Penrose, John F.
a1d34fbc-ff46-49bd-a184-ba20a900239b
Kanaoka, Yoshihide
e972a977-d2b8-4078-b01a-ff6d6423ddcf
Austen, K. Frank
59cdb2b7-ff11-42a0-93db-44f643c065e1
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Sampson, Anthony P.
4ca76f6f-ff35-425d-a7e7-c2bd2ea2df60

Seymour, Michelle L., Rak, Sabina, Aberg, Daniel, Riise, Gert, Penrose, John F., Kanaoka, Yoshihide, Austen, K. Frank, Holgate, Stephen T. and Sampson, Anthony P. (2001) Leukotriene and prostanoid pathway enzymes in bronchial biopsies of seasonal allergic asthmatics. American Journal of Respiratory and Critical Care Medicine, 164 (11), 2051-2056.

Record type: Article

Abstract

Cysteinyl-leukotrienes and prostaglandin D2 generated by the 5-lipoxygenase (5-LO) and cyclooxygenase (COX) pathways, respectively, cause bronchoconstriction, leukocyte recruitment, and bronchial hyperresponsiveness in asthma. We characterized the cellular expression of 5-LO and COX enzymes using immunohistochemistry on bronchial biopsies from 12 allergic asthmatic patients before and during seasonal exposure to birch pollen.

Bronchial responsiveness (p = 0.004) and symptoms (p < 0.005) increased and peak expiratory flow (PEF; p 0.02) decreased in the pollen season. In-season biopsies had 2-fold more cells immunostaining for 5-LO (p = 0.02), 5-LO-activating protein (FLAP; p = 0.04), and leukotriene (LT)A4 hydrolase (p = 0.05), and 4-fold more for the terminal enzyme for cysteinyl-leukotriene synthesis, LTC4 synthase (p = 0.02). Immunostaining for COX-1, COX-2, and PGD2 synthase was unchanged.

Increased staining for LTC4 synthase was due to increased eosinophils (p = 0.035) and an increased proportion of eosinophils expressing the enzyme (p = 0.047). Macrophages also increased (p = 0.019), but mast cells and T-lymphocyte subsets were unchanged. Inverse correlations between PEF and 5-LO+ cell counts link increased expression of 5-LO pathway enzymes in eosinophils and macrophages within the bronchial mucosa to deterioration of lung function during seasonal allergen exposure.




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Published date: December 2001

Identifiers

Local EPrints ID: 40766
URI: http://eprints.soton.ac.uk/id/eprint/40766
ISSN: 1073-449X
PURE UUID: a8f1f418-e27b-4a73-ab4a-4bcd3d75ef06
ORCID for Anthony P. Sampson: ORCID iD orcid.org/0009-0008-9653-8935

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Date deposited: 07 Jul 2006
Last modified: 16 Mar 2024 02:51

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Contributors

Author: Michelle L. Seymour
Author: Sabina Rak
Author: Daniel Aberg
Author: Gert Riise
Author: John F. Penrose
Author: Yoshihide Kanaoka
Author: K. Frank Austen

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