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.
Expression of 5-lipoxygenase and cyclooxygenase pathway enzymes in the nasal polyps of patients with aspirin-intolerant asthma
Journal of Pathology, 209, (3), . (doi:10.1002/path.1979). (PMID:16583357).
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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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