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Expression of 5-lipoxygenase and cyclooxygenase pathway enzymes in the nasal polyps of patients with aspirin-intolerant asthma

Expression of 5-lipoxygenase and cyclooxygenase pathway enzymes in the nasal polyps of patients with aspirin-intolerant asthma
Expression of 5-lipoxygenase and cyclooxygenase pathway enzymes in the nasal polyps of patients with aspirin-intolerant asthma
In aspirin-intolerant subjects, adverse bronchial and nasal reactions to cyclooxygenase (COX) inhibitors are associated with over-production of cysteinyl-leukotrienes (cys-LTs) generated by the 5-lipoxygenase (5-LO) pathway. In the bronchi of patients with aspirin-intolerant asthma, we previously linked cys-LT over-production and aspirin hyper-reactivity with elevated immunoexpression in eosinophils of the terminal enzyme for cys-LT production, LTC4 synthase. We investigated whether this anomaly also occurs in the nasal airways of these patients. Immunohistochemical expression of 5-LO and COX pathway proteins was quantified in nasal polyps from 12 patients with aspirin-intolerant asthma and 13 with aspirin-tolerant asthma. In the mucosa of polyps from aspirin-intolerant asthmatic patients, cells immunopositive for LTC4 synthase were four-fold more numerous than in aspirin-tolerant asthmatic patients (p = 0.04). There were also three-fold more cells expressing 5-LO (p = 0.037), with no differences in 5-LO activating protein (FLAP), COX-1 or COX-2. LTC4 synthase-positive cell counts correlated exclusively with mucosal eosinophils (r = 0.94, p < 0.001, n = 25). Co-localisation confirmed that five-fold higher eosinophil counts (p = 0.007) accounted for the increased LTC4 synthase expression in polyps from aspirin-intolerant asthmatic patients, with no alterations in mast cells or macrophages. Within the epithelium, increased counts of eosinophils (p = 0.006), macrophages (p = 0.097), and mast cells (p = 0.034) in aspirin-intolerant asthmatic polyps were associated only with 2.5-fold increased 5-LO-positive cells (p < 0.05), while the other enzymes were not different. Our results indicate that a marked over-representation of LTC4 synthase in mucosal eosinophils is closely linked to aspirin intolerance in the nasal airway, as in the bronchial airways.
aspirin, asthma, cyclooxygenase, leukotriene, 5-lipoxygenase, nasal polyposis, prostaglandin, non-steroidal anti-inflammatory drugs, LTC4 synthase
1096-9896
392-399
Adamjee, J.
058d1864-3809-48cf-bcd7-fefc76b3ba1f
Suh, Y-J.
98309e1e-379d-4613-9b6a-2820e17fefb8
Park, H-S
7b09d319-8d35-430c-af03-e6f44e689bd3
Choi, J-H
399fd48d-81a0-4fb1-ad20-be3c254cfbe5
Penrose, J.F.
3a1b8c7d-7ea8-4736-80e2-8199e269728e
Lam, B.K.
0373c2e2-94d3-441c-9bb7-b46fdc4942dc
Austen, K.F.
cd543c90-dd9b-427e-88fc-1dbcac8ae02c
Cazaly, A.M.
e9ab0071-5992-481d-b542-9a60b3cfb63d
Wilson, S.J.
21c6875d-6870-441b-ae7a-603562a646b8
Sampson, A.P.
4ca76f6f-ff35-425d-a7e7-c2bd2ea2df60
Adamjee, J.
058d1864-3809-48cf-bcd7-fefc76b3ba1f
Suh, Y-J.
98309e1e-379d-4613-9b6a-2820e17fefb8
Park, H-S
7b09d319-8d35-430c-af03-e6f44e689bd3
Choi, J-H
399fd48d-81a0-4fb1-ad20-be3c254cfbe5
Penrose, J.F.
3a1b8c7d-7ea8-4736-80e2-8199e269728e
Lam, B.K.
0373c2e2-94d3-441c-9bb7-b46fdc4942dc
Austen, K.F.
cd543c90-dd9b-427e-88fc-1dbcac8ae02c
Cazaly, A.M.
e9ab0071-5992-481d-b542-9a60b3cfb63d
Wilson, S.J.
21c6875d-6870-441b-ae7a-603562a646b8
Sampson, A.P.
4ca76f6f-ff35-425d-a7e7-c2bd2ea2df60

Adamjee, J., Suh, Y-J., Park, H-S, Choi, J-H, Penrose, J.F., Lam, B.K., Austen, K.F., Cazaly, A.M., Wilson, S.J. and Sampson, A.P. (2006) Expression of 5-lipoxygenase and cyclooxygenase pathway enzymes in the nasal polyps of patients with aspirin-intolerant asthma. The Journal of Pathology, 209 (3), 392-399. (doi:10.1002/path.1979). (PMID:16583357)

Record type: Article

Abstract

In aspirin-intolerant subjects, adverse bronchial and nasal reactions to cyclooxygenase (COX) inhibitors are associated with over-production of cysteinyl-leukotrienes (cys-LTs) generated by the 5-lipoxygenase (5-LO) pathway. In the bronchi of patients with aspirin-intolerant asthma, we previously linked cys-LT over-production and aspirin hyper-reactivity with elevated immunoexpression in eosinophils of the terminal enzyme for cys-LT production, LTC4 synthase. We investigated whether this anomaly also occurs in the nasal airways of these patients. Immunohistochemical expression of 5-LO and COX pathway proteins was quantified in nasal polyps from 12 patients with aspirin-intolerant asthma and 13 with aspirin-tolerant asthma. In the mucosa of polyps from aspirin-intolerant asthmatic patients, cells immunopositive for LTC4 synthase were four-fold more numerous than in aspirin-tolerant asthmatic patients (p = 0.04). There were also three-fold more cells expressing 5-LO (p = 0.037), with no differences in 5-LO activating protein (FLAP), COX-1 or COX-2. LTC4 synthase-positive cell counts correlated exclusively with mucosal eosinophils (r = 0.94, p < 0.001, n = 25). Co-localisation confirmed that five-fold higher eosinophil counts (p = 0.007) accounted for the increased LTC4 synthase expression in polyps from aspirin-intolerant asthmatic patients, with no alterations in mast cells or macrophages. Within the epithelium, increased counts of eosinophils (p = 0.006), macrophages (p = 0.097), and mast cells (p = 0.034) in aspirin-intolerant asthmatic polyps were associated only with 2.5-fold increased 5-LO-positive cells (p < 0.05), while the other enzymes were not different. Our results indicate that a marked over-representation of LTC4 synthase in mucosal eosinophils is closely linked to aspirin intolerance in the nasal airway, as in the bronchial airways.

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More information

Published date: July 2006
Keywords: aspirin, asthma, cyclooxygenase, leukotriene, 5-lipoxygenase, nasal polyposis, prostaglandin, non-steroidal anti-inflammatory drugs, LTC4 synthase

Identifiers

Local EPrints ID: 40653
URI: https://eprints.soton.ac.uk/id/eprint/40653
ISSN: 1096-9896
PURE UUID: efd33231-c474-471a-81aa-70a8c66e895e

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Date deposited: 07 Jul 2006
Last modified: 28 Jun 2018 16:31

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