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[嗜酸性粒细胞性支气管炎和咳嗽变异性哮喘的气道炎症机制]

[The mechanism of airway inflammation in eosinophilic bronchitis and cough variant asthma].

作者信息

Wang Jiao-Li, Ren Zhen-Yi, Xia Jun-Bo, Huang Sheng, Qi Ming-Hao, Wang Li-Min, Ye Jian

机构信息

Department of Respiratory Medicine, Hangzhou First People's Hospital, Hangzhou 310006, China.

出版信息

Zhonghua Jie He He Hu Xi Za Zhi. 2011 Jun;34(6):433-7.

Abstract

OBJECTIVE

To explore the characteristics of airway inflammatory cells, cytokines and inflammatory mediators in eosinophilic bronchitis (EB) and cough variant asthma (CVA) patients and to elucidate the underlying mechanism of distinct airway inflammation between EB and CVA.

METHODS

This study included 15 patients with EB (EB group), 15 patients with cough variant asthma (CVA, CVA group), 14 patients with bronchial asthma (asthma group) and 14 healthy controls (healthy group). Percentage of eosinophils (EOS) in sputum induced by hypertonic saline was detected by FACS. The percentage of CD(69)(+) EOS stimulated by interleukin-5 (IL-5) and interferon γ (IFN-γ) was also detected by FACS. The expression of leukotriene C4 synthase (LTC4S) and prostaglandin-endoperoxide synthase-2 (PTGS2) mRNA in sputum was measured by real-time PCR and the concentration of leukotriene C4 (LTC4) and prostaglandin E2 (PGE2) in sputum was measured by ELISA.

RESULTS

The percentage of EOS in induced sputum was 15.8 ± 3.2 (EB group), 13.0 ± 2.7 (CVA group) and 11.6 ± 4.5 (asthma group), respectively, which were significantly higher than 1.0 ± 0.4 in the healthy group. The difference was significant and the t value was 16.31, 15.23 and 14.21 respectively (P < 0.05). After stimulated by IL-5 and IFN-γ, the percentage of CD(69)(+) EOS in induced sputum was 1.5 ± 0.4 and 1.5 ± 0.5 (EB group), 1.4 ± 0.4 and 1.4 ± 0.3 (CVA group) and 1.42 ± 0.72 and 1.37 ± 0.46 (asthma group) respectively. There was no statistical significance between these 3 groups, but when compared with 0.4 ± 0.2 and 0.4 ± 0.1 in healthy group, the difference was significant (P < 0.05). The expression of IL-5 mRNA and protein in induced sputum of EB group, CVA group and asthma group were higher than the healthy group and the difference was all statistically different (P < 0.05), but there was no statistical significance between EB group, CVA group and asthma group. The expression of IFN-γ mRNA and protein in induced sputum of each group was not different when compared with healthy group (P > 0.05). The concentration of PGE2 in induced sputum of EB group was(839 ± 69) ng/L, which was higher than (33 ± 8) ng/L of CVA group, (25 ± 6) ng/L of asthma group and (24 ± 8) ng/L of healthy group (all P < 0.01). There was no statistical difference between CVA group, asthma group and healthy group. The expression of PTGS2 in induced sputum of EB group increased significantly; when compared with CVA group, asthma group and healthy group, the difference was significant (all P < 0.01). The concentration of LTC4 in induced sputum of EB group, CVA group and asthma group was all higher than the healthy group (all P < 0.05). The expression of LTC4S mRNA of EB group, CVA group and asthma group was also higher than the healthy group (all P < 0.05). The expression of LTC4S mRNA and LTC4 in the EB group was higher than that in the CVA group and the asthma group (P < 0.05). The value of LTC4/PGE2 in the CVA group and the asthma group was higher than that in the EB group (t = 8.7 and 13.1, P < 0.05).

CONCLUSION

These data suggest that the difference in airway function observed in subjects with eosinophilic bronchitis and CVA (or asthma) may be due to the results of differences in PGE(2) production and an imbalance between the production of bronchoconstrictor LTC(4) and bronchoprotective PGE(2) lipid mediators.

摘要

目的

探讨嗜酸性粒细胞性支气管炎(EB)和咳嗽变异性哮喘(CVA)患者气道炎症细胞、细胞因子及炎症介质的特征,阐明EB与CVA气道炎症差异的潜在机制。

方法

本研究纳入15例EB患者(EB组)、15例咳嗽变异性哮喘患者(CVA组)、14例支气管哮喘患者(哮喘组)和14例健康对照者(健康组)。采用流式细胞术检测高渗盐水诱导痰中嗜酸性粒细胞(EOS)百分比。同样采用流式细胞术检测白细胞介素-5(IL-5)和干扰素γ(IFN-γ)刺激后诱导痰中CD(69)(+) EOS百分比。采用实时荧光定量PCR检测痰中白三烯C4合成酶(LTC4S)和前列腺素内过氧化物合酶-2(PTGS2)mRNA表达,采用酶联免疫吸附测定法检测痰中白三烯C4(LTC4)和前列腺素E2(PGE2)浓度。

结果

诱导痰中EOS百分比在EB组为15.8±3.2,CVA组为13.0±2.7,哮喘组为11.6±4.5,均显著高于健康组的1.0±0.4。差异有统计学意义,t值分别为16.31、15.23和14.21(P<0.05)。IL-5和IFN-γ刺激后,诱导痰中CD(69)(+) EOS百分比在EB组分别为1.5±0.4和1.5±0.5,CVA组分别为1.4±0.4和1.4±0.3,哮喘组分别为1.42±0.72和1.37±0.46。这3组之间无统计学差异,但与健康组的0.4±0.2和0.4±0.1相比,差异有统计学意义(P<0.05)。EB组、CVA组和哮喘组诱导痰中IL-5 mRNA和蛋白表达均高于健康组,差异均有统计学意义(P<0.05),但EB组、CVA组和哮喘组之间无统计学意义。各组诱导痰中IFN-γ mRNA和蛋白表达与健康组相比无差异(P>0.05)。EB组诱导痰中PGE2浓度为(839±69)ng/L,高于CVA组的(33±8)ng/L、哮喘组的(25±6)ng/L和健康组的(24±8)ng/L(均P<0.01)。CVA组、哮喘组和健康组之间无统计学差异。EB组诱导痰中PTGS2表达显著增加;与CVA组、哮喘组和健康组相比,差异有统计学意义(均P<0.01)。EB组、CVA组和哮喘组诱导痰中LTC4浓度均高于健康组(均P<0.05)。EB组、CVA组和哮喘组LTC4S mRNA表达也高于健康组(均P<0.05)。EB组LTC4S mRNA和LTC4表达高于CVA组和哮喘组(P<0.05)。CVA组和哮喘组LTC4/PGE2值高于EB组(t=8.7和13.1,P<0.05)。

结论

这些数据表明,嗜酸性粒细胞性支气管炎和CVA(或哮喘)患者气道功能的差异可能是由于PGE(2)产生的差异以及支气管收缩剂LTC(4)和支气管保护剂PGE(2)脂质介质产生失衡的结果。

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