糖皮质激素和茶碱对慢性阻塞性肺疾病患者外周血T细胞表达CXCR3的影响
The effects of glucocorticoids and theophylline on CXCR3 expression of peripheral blood T cell in COPD patients
摘要目的 探讨糖皮质激素和茶碱对慢性阻塞性肺疾病(COPD)患者T细胞表达CXCR3的作用. 方法 选取2009年3月至2011年1月未行治疗的COPD稳定期门诊患者21例,男18例、女3例,年龄(66.4±4.2)岁,第1秒用力呼吸量(FEV1)占预计值百分比为(60.8±7.2)%.取外周血单个核细胞,分为4组处理,分别与5 mg/L及15 mg/L氨茶碱、10 nmol/L及100 nmol/L的布地奈德共培养48 h,流式细胞仪检测CD8+T及CD4+T淋巴细胞表面CXCR3的表达,计算CD8+CXCR3+T细胞百分比(CD8+CXCR3+T细胞/CD8+T细胞)、CD4+CXCR3+T细胞百分比(CD4+CXCR3+T细胞/CD4+T细胞)及其相应的平均荧光强度(MFI). 结果 5 mg/L及15 mg/L氨茶碱作用下CD8+CXCR3+T细胞百分比、CD4+CXCR3+T细胞百分比及CD8+CXCR3+T细胞MFI与空白对照组比较差异无统计学意义;CD4+ CXCR3+T细胞MFI(83.40±15.20和79.11±18.81)与空白对照组98.90±17.45比较有明显降低(F=7.676,P=0.001),5 mg/L氨茶碱组与15 mg/L氨茶碱组比较差异无统计学意义(P>0.05).10 nmol/L及100 nmol/L布地奈德作用下CD8+CXCR3+T细胞百分比[(41.05±14.27)%和(34.85±11.63)%]、CD4+ CXCR3+T细胞百分比[(29.96±8.33)%和(26.27±7.34)%]、CD8+ CXCR3+T细胞MFI(65.56±15.43和62.11±16.49)及CD4+ CXCR3+T细胞MFI(69.66±15.37和63.75±14.29)均较空白对照组[(58.64±18.95)%、(37.11±11.70)%、84.92±19.79、98.90±17.45]降低(F=13.597、7.350、10.569、29.959,P=0.000、0.001、0.000、0.000);两种不同浓度布地奈德组比较差异无统计学意义(均P>0.05). 结论 小剂量或常规剂量氨茶碱抗炎作用可能与CD8+T细胞CXCR3识别趋化因子能力无关,但可使CD4+T细胞识别趋化因子能力减弱;糖皮质激素布地奈德则使T细胞识别趋化因子能力减弱.
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abstractsObjective To investigate the effects of glucocorticoid and theophylline on CXCR3 expression of peripheral blood T cell in chronic obstructive pulmonary disease(COPD) patients.Methods Twenty-one patients(18 males and 3 females,aged 66.42±4.20 years in average,FEV1/ prediction value of(60.8±t7.2) % with stable COPD and no treatment were recruited from March 2009 to January 2011.Peripheral blood mononuclear cells were isolated by density gradient centrifugation and cultivated respectively with 5 mg/L and 15 mg/L aminophylline,10 nmol/L and 100 nmol/L of budesonide for 48 hours.Flow cytometry was applied to evaluate the expression level of CXCR3 on CD4+ and CD8+ T cells surface,and to calculate the percentage of CD4+ CXCR3+ cells over total CD4+ cells(CD4+ CXCR3+ T cells/CD4+ T cells)and the percentage of CD8+ CXCR3+ T cells over total CD8 + cells(CD8 + CXCR3 + T cells/CD8+ T cells),and to detect the mean fluorescence intensity (MFI) of CXCR3+ on CD4+ and CD8+ cells from the different groups.Results There were no statistically significant differences between 5 mg/L or 15 mg/L aminophylline group and the control group in percentages of CD4+ CXCR3+ cells over the total CD4+ cells,of CD8+ CXCR3+ cells over the total CD8+ cells,and the MFI of CXCR3 on CD8+ cells(all P>0.05).However,MFI of CXCR3+ on CD4+ cells were markedly decreased in two aminophylline groups versus the control group(P<0.01).There was no significant difference between two aminophylline groups(P>0.05).The 10 nmol/L and 100 nmol/L of budesonide treatment group showed the markedly decreased levels of percentages of CD4+ CXCR3+ cells over the total CD4+ cells,of CD8+ CXCR3+ cells over the total CD8+ cells and the MFI of CXCR3+ on CD4+ and CD8+ cells,as compared with control group (F =13.597,7.350,10.569,29.959,P=0.000,0.001,0.000,0.000).There was no statistically significant difference between two budesonide groups (P>0.05).Conclusions Small dose or routine dose of aminophylline has no effect on the expression of CXCR3 on CD8+ T cells,but down+regulates the expression of CXCR3 on CD4+ T cells.Glucocorticoid budesonide down-regulates the expression of CXCR3 on T cells.
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