Expression of cysteinyl leukotriene synthetic and signalling proteins in inflammatory cells in active seasonal allergic rhinitis

被引:103
作者
Figueroa, DJ
Borish, L
Baramki, D
Philip, G
Austin, CP
Evans, JF
机构
[1] Merck Res Labs, Dept Neurosci, West Point, PA 19486 USA
[2] Univ Virginia Hlth Syst, Asthma & Allerg Dis Ctr, Charlottesville, VA USA
[3] Merck Res Labs, Dept Resp & Allergy, Rahway, NJ USA
[4] Merck Res Labs, Dept Pharmacol, West Point, PA USA
关键词
airway inflammation; allergic rhinitis; immunology; leukotriene receptor biology;
D O I
10.1046/j.1365-2222.2003.01786.x
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background Cysteinyl leukotrienes (CysLTs) are bioactive lipids that have been shown to contribute to allergic and inflammatory diseases. Eosinophils and mast cells have the capacity to produce large amounts of CysLTs after allergic or non-allergic stimulation. Molecular identification of both the synthetic and signalling proteins in the CysLT pathway allows the investigation of expression of the CysLT enzymes and receptors in active allergic rhinitis. Objective We examined the expression of the proteins involved in the synthesis of CysLTs and the cysteinyl leukotriene-1 (CysLT(1)) and cysteinyl leukotriene-2 (CysLT(2)) receptors in inflammatory cells from patients with active seasonal allergic rhinitis. Methods Nasal lavage samples were obtained from patients during active seasonal allergic rhinitis. Specific cellular immunocytochemical techniques were used to detect the cysteinyl leukotriene synthetic proteins, namely 5-lipoxygenase (5-LO), 5-lipoxygenase-activating protein (FLAP) and leukotriene C-4 synthase (LTC4S). In situ hybridization and immunocytochemical techniques were used to identify the mRNA and proteins for the CysLT1 and CysLT2 receptors. Results 5-LO, FLAP and LTC4S, and the CysLT(1) and CysLT(2) receptors were expressed in the majority of eosinophils and in subsets of mast cells and mononuclear cells. 5-LO, FLAP and the CysLT1 receptor, but not LTC4S or the CysLT2 receptor, were expressed in a subset of nasal neutrophils. Conclusions Our study demonstrates the presence of CysLT pathway proteins in key allergic and inflammatory cells from the upper airway of patients with active seasonal allergic rhinitis. Our expression data highlight the potential of CysLT-modifying agents to treat both upper and lower airway symptoms in patients suffering from allergic rhinitis and asthma.
引用
收藏
页码:1380 / 1388
页数:9
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