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

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. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.