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1-磷酸鞘氨醇受体表达在变应性鼻炎患者嗜酸性粒细胞中的作用及鼻用糖皮质激素治疗对该受体表达的影响。

Role of sphingosine 1-phosphate receptor expression in eosinophils of patients with allergic rhinitis, and effect of topical nasal steroid treatment on this receptor expression.

作者信息

Mackle T, Gendy S S, Walsh M, McConn-Walsh R, Costello R W, Walsh M-T

机构信息

Department of Otorhinolaryngology, Beaumont Hospital, Dublin, Ireland.

出版信息

J Laryngol Otol. 2008 Dec;122(12):1309-17. doi: 10.1017/S0022215108003241. Epub 2008 Sep 23.

Abstract

OBJECTIVE

Recent research has indicated that sphingosine 1-phosphate plays a role in allergy. This study examined the effect of allergen challenge on the expression of sphingosine 1-phosphate receptors on the eosinophils of allergic rhinitis patients, and the effect of steroid treatment on this expression.

STUDY DESIGN

A prospective, non-randomised study.

METHODS

The study had three parts. Firstly, sphingosine 1-phosphate receptor expression on the eosinophils of allergic rhinitis patients and control patients was determined. Secondly, sphingosine 1-phosphate receptor expression was quantified pre- and post-allergen challenge, before and after a short course of fluticasone propionate; all patients underwent symptom scoring and peak nasal inspiratory flow measurement pre- and post-allergen challenge, both before and after steroid or saline treatment. Thirdly, the effect of sphingosine 1-phosphate on eosinophil migration was examined.

RESULTS

The eosinophils of both allergic rhinitis patients and controls expressed sphingosine 1-phosphate1, 3, 4, and 5. Eosinophils from all allergic rhinitis patients demonstrated up-regulation in sphingosine 1-phosphate expression after allergen challenge. These changes were statistically very significant for sphingosine 1-phosphate1, 4, and 5, and moderately significant for sphingosine 1-phosphate3. Sphingosine 1-phosphate receptor expression up-regulation was abolished in the steroid-treated group after allergen challenge; however, the saline-treated group showed no change in sphingosine 1-phosphate receptor expression after allergen challenge. Peak nasal inspiratory flow scores were significantly diminished after allergen challenge prior to treatment, but not after a course of topical nasal steroids. Sphingosine 1-phosphate induced eosinophil chemotaxis was increased following allergen challenge in allergic rhinitis subjects.

CONCLUSIONS

Local intranasal steroid therapy acts directly to block allergen-induced up-regulation of sphingosine 1-phosphate receptors on the peripheral eosinophils of allergic rhinitis patients, and this is coincident with post-challenge peak nasal inspiratory flow measurement improvements. These observations support the idea that such an increase in sphingosine 1-phosphate receptor expression is clinically relevant in allergic rhinitis, with potential consequences for eosinophil migration and survival.

摘要

目的

近期研究表明,1-磷酸鞘氨醇在过敏反应中起作用。本研究检测了变应原激发对过敏性鼻炎患者嗜酸性粒细胞上1-磷酸鞘氨醇受体表达的影响,以及类固醇治疗对该表达的影响。

研究设计

一项前瞻性、非随机研究。

方法

本研究分为三个部分。首先,测定过敏性鼻炎患者和对照患者嗜酸性粒细胞上1-磷酸鞘氨醇受体的表达。其次,在变应原激发前后、丙酸氟替卡松短期治疗前后对1-磷酸鞘氨醇受体表达进行定量;所有患者在变应原激发前后、类固醇或盐水治疗前后均进行症状评分和鼻吸气峰流量测量。第三,检测1-磷酸鞘氨醇对嗜酸性粒细胞迁移的影响。

结果

过敏性鼻炎患者和对照患者的嗜酸性粒细胞均表达1-磷酸鞘氨醇1、3、4和5。所有过敏性鼻炎患者的嗜酸性粒细胞在变应原激发后1-磷酸鞘氨醇表达上调。这些变化在1-磷酸鞘氨醇1、4和5方面具有统计学意义,在1-磷酸鞘氨醇3方面具有中度意义。变应原激发后,类固醇治疗组的1-磷酸鞘氨醇受体表达上调被消除;然而,盐水治疗组在变应原激发后1-磷酸鞘氨醇受体表达无变化。治疗前变应原激发后鼻吸气峰流量评分显著降低,但局部鼻用类固醇治疗后未降低。变应原激发后,过敏性鼻炎患者中1-磷酸鞘氨醇诱导的嗜酸性粒细胞趋化性增加。

结论

局部鼻内类固醇治疗直接作用于阻断变应原诱导的过敏性鼻炎患者外周嗜酸性粒细胞上1-磷酸鞘氨醇受体的上调,这与激发后鼻吸气峰流量测量的改善相一致。这些观察结果支持这样一种观点,即1-磷酸鞘氨醇受体表达的这种增加在过敏性鼻炎中具有临床相关性,对嗜酸性粒细胞迁移和存活可能产生影响。

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