Th17淋巴细胞及相关细胞因子加重哮喘小鼠气道炎症  

Roles of Th17 lymphocytes and inflammatory cytokines in airway inflammation exacerbation of murine asthmatic model

作　　者：李鸿佳[1] 张才擎[1] 于翠香[1] 刘粉[1] 盖庆玲[2] 吴金香[3] 赵继平[3] 董亮[3] 

机构地区：[1]山东大学附属省千佛山医院呼吸科,山东济南250014 [2]山东省胸科医院内科,山东济南250013 [3]山东大学齐鲁医院呼吸科,山东济南250012

出　　处：《细胞与分子免疫学杂志》2012年第11期1126-1128,1132,共4页Chinese Journal of Cellular and Molecular Immunology

基　　金：山东省自然科学基金(ZR2009CQ018)

摘　　要：目的:研究Th17淋巴细胞及其相关的细胞因子在加重哮喘小鼠气道炎症中的作用机制。方法:20只小鼠随机均分为哮喘组和正常对照组。哮喘组用卵白蛋白(OVA)致敏与激发建立小鼠哮喘模型。对照组致敏与激发均以生理盐水代替。HE染色观察小鼠气道及肺组织病理变化;光学显微镜下观察小鼠支气管肺泡灌洗液(BALF)中细胞分类及计数;酶联免疫吸附试验(ELISA)检测小鼠BALF上清中IL-4、IFN-γ及IL-17的含量,流式细胞技术(FCM)检测小鼠外周血Th1、Th2及Th17淋巴细胞占CD4+细胞百分率情况。将外周血各T淋巴细胞亚群与BALF的中性粒细胞数作相关性分析。结果:哮喘组小鼠BALF中细胞数及中性粒细胞、嗜酸性粒细胞、淋巴细胞百分率均显著高于对照组(P<0.05),BALF上清中IL-4和IL-17的水平显著增高(P<0.05),而IFN-γ的水平显著降低(P<0.05),外周血Th2、Th17淋巴细胞占CD4+细胞百分比显著增高(P<0.05),而Th1淋巴细胞占CD4+细胞百分比显著降低(P<0.05)。相关性分析显示Th1淋巴细胞与BALF的中性粒细胞数呈显著负相关(rTh1=-0.446,P<0.05),Th17淋巴细胞与BALF的中性粒细胞数呈显著正相关(rTh17=0.394,P<0.05)。结论:Th17淋巴细胞可促进中性粒细胞及炎性介质在哮喘小鼠气道内的聚集,加重气道炎症。AIM： To investigate the roles of Th17 lymphocytes and its inflammatory cytokines in airway inflam- mation exacerbation of murine asthmatic model. METH- ODS： Twenty mice were randomized into control group and asthma group. For the murine asthma model, the mice were sensitized and challenged with ovalbumin （OVA）. The control mice were given normal saline alone under the same conditions as the asthma group. We observed the changes in cellular proportions in the bronchoalveolar lavage fluid （BALF） under a light microscope and the histological chan- ges in lung tissue by HE staining. The levels of IL-4, IFN-y and IL-17 were detected by ELISA. Th1, Th2 and Th17 cells in the peripheral blood were detected by flow cytometry. We did a correlation analysis between Th1, Th2 and Th17 cells in the peripheral blood and neutrophils in BALF. RESULTS： The total cell number and the percentages of neutrophiis, eosinophils and lymphocytes in BALF of the asthmatic mice were significantly higher than those in the control mice （P 〈 0.05）. The neutrophils and eosinophils infiltration in pulmonary tissue was also dramatically detected in asthmatic mice. The levels of IL-4 and IL-17 were significantly higher thanthose in the control mice （P〈0.05）, while the level of IFN- y was much lower than in the control mice （ P 〈 0.05 ）. Besides, the percentages of Th2 and Tht7 cells in peripheral blood were significantly higher in the asthmatic mice than in the control mice （ P 〈 0.05）. The expression of Th17 was positively correlated with the levels of neutrophils in BALF （ rTh17 = 0. 394, P 〈 0.05 ）, and the expression of Th1 was negatively correlated with the level of neutrophils in BALF （rTh1 = - 0. 446, P 〈 0. 05）. CONCLUSION： Th17 cells could induce the recruitment of inflammatory cytokines and neutrophils into airways, which might aggravate the asthmatic inflammation and be related with asthma exacerbation.

关 键 词：支气管哮喘 细胞因子 T淋巴细胞 气道炎症 急性加重 

分 类 号：R392.11[医药卫生—免疫学]