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Nasal mucosal expression of the leukotriene and prostanoid pathways in seasonal and perennial allergic rhinitis.

机译:季节性和多年生变应性鼻炎中白三烯和前列腺素途径的鼻黏膜表达。

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BACKGROUND: Leukotrienes (LTs) and prostanoids are potent pro-inflammatory and vasoactive lipid mediators implicated in airway disease, but their cellular sources in the nasal airway in naturally occurring allergic rhinitis (AR) are unclear. OBJECTIVE: To quantify cellular expression of enzymes of the 5-lipoxygenase (5-LO) and cyclooxygenase (COX) pathways by immunohistochemistry in nasal biopsies from patients with symptomatic perennial AR (PAR, n = 13) and seasonal AR (SAR, n = 14) and from normal subjects (n = 12). METHODS: Enzymes of the 5-LO pathway (5-LO, FLAP, LT A4 hydrolase, LTC4 synthase) and the COX pathway (COX-1, COX-2, prostaglandin D2 synthase) were immunostained in glycol methacrylate resin-embedded inferior turbinate biopsy specimens, quantified in the lamina propria and epithelium, and co-localized to leucocyte markers by camera lucida. RESULTS: In the lamina propria of PAR biopsies, median counts of cells expressing FLAP were fourfold higher than in normal biopsies (Mann-Whitney, P = 0.014), and also tended to be higher than in SAR biopsies (P = 0.06), which were not different from normal. PAR biopsies showed threefold more cells immunostaining for LTC4 synthase compared with SAR biopsies (P = 0.011) but this was not significant compared with normal biopsies (P = 0.2). These changes were associated with ninefold more eosinophils (P = 0.0005) with no differences in other leucocytes. There were no significant differences in the lamina propria in immunostaining for 5-LO, LTA4 hydrolase, COX-1, COX-2 or PGD2 synthase. Within the epithelium, increased expression of COX-1 was evident in PAR biopsies (P = 0.014) and SAR biopsies (P = 0.037), associated with more intra-epithelial mast cells in both rhinitic groups (P < 0.02). CONCLUSIONS: In the nasal biopsies of PAR subjects, increased expression of regulatory enzymes of the cysteinyl-LT biosynthetic pathway was associated with lamina propria infiltration by eosinophils. Seasonal rhinitis biopsies shared only some of these changes, consistent with transient disease. Increased intra-epithelial mast cells and epithelial COX-1 expression in both rhinitic groups may generate modulatory prostanoids.
机译:背景:白三烯(LTs)和类前列腺素是强力的促炎和血管活性脂质介质,与气道疾病有关,但在自然发生的变应性鼻炎(AR)中,它们在鼻道中的细胞来源尚不清楚。目的:通过免疫组织化学定量分析有症状常年性AR(PAR,n = 13)和季节性AR(SAR,n =)患者鼻活检中5-脂氧合酶(5-LO)和环氧合酶(COX)途径的酶的细胞表达14)和正常受试者(n = 12)。方法:将5-LO途径的酶(5-LO,FLAP,LT A4水解酶,LTC4合酶)和COX途径的酶(COX-1,COX-2,前列腺素D2合酶)用甲基丙烯酸乙二醇酯树脂包埋的下鼻甲进行免疫染色。活检标本,在固有层和上皮中定量,并通过照相机lucida共定位于白细胞标记。结果:在PAR活检的固有层中,表达FLAP的细胞的中位数比正常活检高出四倍(Mann-Whitney,P = 0.014),并且也往往比SAR活检高(P = 0.06)。与正常情况没有什么不同。 PAR活检显示,与SAR活检相比,对LTC4合酶的细胞免疫染色增加了三倍(P = 0.011),但与正常活检相比(P = 0.2)并不显着。这些变化与嗜酸性粒细胞增加了九倍(P = 0.0005),其他白细胞没有差异。在5-LO,LTA4水解酶,COX-1,COX-2或PGD2合酶的免疫染色中,固有层没有显着差异。在上皮内,PAR活检(P = 0.014)和SAR活检(P = 0.037)中COX-1的表达明显增加,这与两个鼻炎组的上皮内肥大细胞相关(P <0.02)。结论:在PAR受试者的鼻活检中,半胱氨酸-LT生物合成途径的调节酶表达增加与嗜酸性粒细胞浸润固有层有关。季节性鼻炎活检仅分享其中一些变化,与短暂性疾病一致。鼻基组中上皮内肥大细胞增加和上皮COX-1表达可能产生调节性前列腺素。

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