Rhinitis, sinusitis, and ocular diseases
Expression of the cysteinyl leukotriene receptors cysLT1 and cysLT2 in aspirin-sensitive and aspirin-tolerant chronic rhinosinusitis

https://doi.org/10.1016/j.jaci.2004.10.051Get rights and content

Background

Cysteinyl leukotrienes play a disease-regulating role in rhinosinusitis and asthma, particularly aspirin-sensitive disease. They act through 2 G-protein coupled receptors termed cysteinyl leukotriene type 1 receptor (cysLT1) and cysteinyl leukotriene type 2 receptor (cysLT2). We previously compared expression of cysLT1 on mucosal leukocytes in patients with aspirin-sensitive and aspirin-tolerant rhinosinusitis.

Objective

To compare expression of cysLT1 and cysLT2 on leukocytes, mucus glands, and epithelium in 32 patients with chronic polypoid rhinosinusitis (21 aspirin-sensitive, 11 aspirin-tolerant) and 9 normal controls.

Methods

Total numbers of CD45+ leukocytes, percentages of these cells expressing cysLT1 or cysLT2, and percentages of the total epithelial and glandular areas expressing cysLT1 or cysLT2 were measured in sections of nasal biopsies by using immunohistochemistry and image analysis.

Results

The percentages of mucosal CD45+ leukocytes expressing cysLT1 were significantly (P < .0001) elevated in the aspirin-sensitive but not the aspirin-tolerant patients compared with the controls. In contrast, the percentages of leukocytes expressing cysLT2 did not differ significantly in the 3 groups. On epithelial and glandular cells, expression of cysLT2 significantly exceeded that of cysLT1 in both the patients with rhinosinusitis and the controls (P ≤ .004), although there was no significant difference in the expression of either receptor in the patients with rhinosinusitis (aspirin-sensitive or aspirin-tolerant) and the controls.

Conclusion

Although cysLT1 expression predominates on inflammatory leukocytes in patients with aspirin-sensitive rhinosinusitis, the effects of cysteinyl leukotrienes on glands and epithelium may be mediated predominantly through cysLT2. This has potentially important therapeutic implications.

Section snippets

Patients

Nasal biopsy specimens were obtained from 32 patients with chronic rhinosinusitis, as defined by the presence of nasal polyps, and 9 normal control subjects with a lifelong absence of perennial or seasonal nasal symptoms. Of the patients with rhinosinusitis, 21 were aspirin-sensitive, and 11 were aspirin-tolerant. Eighteen of the 21 aspirin-sensitive patients, 8 of the 11 tolerant-patients, and 7 of the 9 normal controls were atopic as defined by a positive skin prick test to 1 or more of a

Expression of cysLT1 and cysLT2 on nasal mucosal leukocytes

The absolute numbers of CD45+ leukocytes as well as percentages of these cells expressing cysLT1 and cysLT2 in all of the patients with chronic rhinosinusitis assessed as a single group and normal controls are shown in Fig 1. Significantly elevated percentages of nasal mucosal leukocytes expressed cysLT1 but not cysLT2 in the patients with rhinosinusitis compared with the normal controls (cysLT1 controls: median, 4.2; range, 0.9-15.6; rhinitis: median, 18.0; range, 2.2-51.8; P = .002; cysLT2

Discussion

We have shown in this study that elevated expression of cysLT1 on nasal mucosal inflammatory leukocytes is a phenomenon confined to aspirin-sensitive patients with rhinosinusitis. In contrast, these same cells showed no evidence of upregulation of cysLT2 in patients with rhinosinusitis, whether aspirin-sensitive or aspirin-tolerant, compared with controls. These data considerably extend our previous study.15

The data in this and our previous study15 confirm that subsets of leukocytes of all

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