Expression of Arachidonate Metabolism Enzymes and Receptors in Nasal Polyps of Aspirin-Hypersensitive Asthmatics

Abstract

Background: The pathogenesis of rhinosinusitis in aspirin-exacerbated airway disease is closely linked to the disequilibrium in arachidonic acid metabolism. Although considerable amounts of data concerning impaired eicosanoid production are available, the precise mechanism and pathogenesis of the disease are still unknown. The aim of the present study was to assess the expression of enzymes belonging to the arachidonic acid cascade and receptors for arachidonate derivative metabolites in nasal polyps from aspirin- hypersensitive (AH) and aspirin-tolerant (AT) patients with rhinosinusitis. Methods: Cells expressing cysteinyl leukotriene (CysLT) receptors (CysLT₁ and CysLT₂), arachidonate 5-lipoxygenase, leukotriene B₄ receptor type 1, E-prostanoid receptors (EP₂ and EP₄), cyclooxygenase (COX)-1 and COX-2 were detected by immunocytochemistry in nasal polyps obtained from 10 AH patients and 18 AT patients. Results: There was a significantly higher density of cells expressing CysLT₁ and CysLT₂ receptors in nasal polyps from AH patients than from AT patients (p < 0.001). In contrast, the density of cells expressing EP₂ receptor and COX-2 was significantly lower in AH patients than in AT patients (p < 0.02). The number of COX-2-positive epithelial cells was significantly reduced in AH polyps (p < 0.04). Conclusions: The elevated number of nasal polyp cells expressing CysLT receptors and lack of cells expressing EP₂ receptor and COX-2 may be related to a more severe course of hyperplastic rhinosinusitis in aspirin hypersensitivity.

Impaired E Prostanoid2 Expression and Resistance to Prostaglandin E2 in Nasal Polyp Fibroblasts from Subjects with Aspirin-Exacerbated Respiratory Disease

“…types in AERD (6,12,(14)(15)(16). PGE 2 is a potent inhibitor of fibroblast proliferation primarily by stimulating cyclic AMP accumulation and exchange protein activated by cyclic AMP (EPAC) through EP 2 receptors (17).…”

Upper airways in aspirin-exacerbated respiratory disease

“…Moreover, remarkable reductions in urinary leukotriene (LT) C 4 levels have been reported after endoscopic sinus surgery to treat CRSwNP in AERD patients [10]; this may be a consequence of debulking of sinus CysLT-producing cells. Enhanced production of CysLTs in CRSwNP tissue is associated with elevated expression of LTC 4 synthase, the ratelimiting enzyme in CysLT biosynthesis [11]. Higher level expression of CysLT receptors, including both CysLT receptor 1 (CysLTR1) and CysLTR2, was also evident in the CRSwNP mucosal tissue of AERD patients, compared with those with ATA [11][12][13].…”

“…Enhanced production of CysLTs in CRSwNP tissue is associated with elevated expression of LTC 4 synthase, the ratelimiting enzyme in CysLT biosynthesis [11]. Higher level expression of CysLT receptors, including both CysLT receptor 1 (CysLTR1) and CysLTR2, was also evident in the CRSwNP mucosal tissue of AERD patients, compared with those with ATA [11][12][13]. PGE 2 exerts both an anti-inflammatory effect and a bronchoprotective role, and its antiinflammatory effects are induced via stimulation of the E-prostanoid (EP)2 receptor [14].…”

The Intervention of CRAC Channels Alleviates Inflammatory Responses in Nasal Polyps

“…Many studies indicate mast cell abundance and distribution in NP [28], and show that chemical mediators such as LTC4 degranulation from the cells can produce profound tissue edema [29,30]. LTC4 and LTC4S mRNA were all enhanced in the polyp cultures in comparison with those in the normal mucosa cultures (fig.…”