脂多糖诱导髓源抑制性细胞对哮喘小鼠气道炎症的影响及其机制  

Effect and mechanism of lipopolysaccharides-induced myeloid-derived suppressor cells on airway inflanunation in asthmatic mice

作　　者：郑燕妮[1] 于化鹏[1] 陈新[1] 邓火金[1] 樊慧珍[1] 龚雨新[1] 方泽葵[1] 

机构地区：[1]南方医科大学珠江医院呼吸内科,广州510282

出　　处：《中华医学杂志》2012年第44期3147-3150,共4页National Medical Journal of China

基　　金：广东省科技计划项目（2010B031600095）

摘　　要：目的探讨脂多糖诱导的髓源抑制性细胞对哮喘小鼠气道炎症的影响及其机制。方法雌性BALB／c小鼠34只，其中4只接受脂多糖注射以诱导髓源抑制性细胞募集，采用CD11b磁珠从脾脏中分选该群细胞，其余30只随机数字表法分为对照组、哮喘组和治疗组。哮喘组和治疗组给予卵白蛋白致敏并雾化吸入建立哮喘模型。治疗组在诱导哮喘第14天及第21天分别注入体外磁珠分离的髓源抑制性细胞。各组在末次激发24h内计数支气管肺泡灌洗液（BALF）中细胞总数并分类，结合病理切片分析气道炎症情况；采用酶联免疫吸附（ELISA）法检测BALF和血清中白细胞介素13（IL-13）的变化；流式细胞仪检测外周血CD4^＋CD25^＋Foxp3^＋调节性T细胞（简称Treg细胞）的比例。结果治疗组BALF中细胞总数、中性粒细胞、嗜酸粒细胞百分比[（17．0±8．3）×10^4／ml、11．1％±2．0％、9．8％±2．9％]显著低于哮喘组[（36．0±15．9）×10^4／ml、20．8％±4．0％、14．1％±4．2％]（P=0．000、0．000、0．011），BALF和血清中IL-13含量[（34．7±7．1）和（34．0±4．7）ng／L]显著低于哮喘组[（105．0±9．0）和（48．1±6．1）ng／L]（均P=0．000），外周血Treg细胞的比例（8．0％±1．3％）高于哮喘组（5．1％±2．1％）（P=0．002）；治疗组气道炎症较哮喘组轻。结论脂多糖来源的髓源抑制性细胞可能通过抑制Th2过度免疫应答和上调小鼠外周血Treg细胞比例，从而减轻哮喘小鼠气道炎症。Objective To explore the effect and mechanism of lipopolysaccharides （LPS）-induced CD11^＋Gr-1^＋ myeloid-derived suppressor cells （MDSCs） on airway inflammation in asthmatic mice. Methods A total of 34 female BALB/c mice were selected. Among them, 4 mice received an intraperitoneal injection of LPS for inducing the accumulation of MDSCs. And the MDSCs were separated with CD11b immunomagnetic beads from spleen extract. Another 30 mice were randomly divided into normal control, asthmatic and cell treatment groups. The mice in the asthmatic and cell treatment groups were sensitized with ovalbumin by a combination of intraperitoneal injection and challenges to establish the murine asthmatic model. At Days 14 and 21 post-sensitization, the mice in cell treatment group received an intravenous injection of LPS-induced MDSCs. At 24 hours after the last allergen challenge, the number of inflammatory cells were counted and morphological identification of leucocytes in bronchoalveolar lavage fluid （BALF） was performed to analyze the degree of airway inflammation in conjunctions with pathological sections. The BALF and serum levels of interleukin-13 were measured by enzyme-linked immunosorbnent assay （ELISA）. The number of CD4^＋CD25^＋Foxp3^＋ regulatory T cells （Tregs） in peripheral blood was measured by flow cytometry. Results The total number of cells, the percentage of neutrophils and eosinophils of BALF in the cell treatment group [ （ 17.0 ±8.3） × 104/ml, 11.1% ±2. 0%, 9. 8% ±2. 9% ] were significantly lower than those in the asthmatic group [ （ 36. 0 ±15.9） × 10^4/ml, 20. 8% ± 4. 0%, 14. 1% ±4. 2% ] （P =0. 000, 0. 000, 0. 011 ）. Compared to the asthmatic group, the BALF and serum levels of IL-13 were significantly lower [ （34. 7 ±7. 1 ） vs （ 105.0 ±9. 0） ng/L, （34. 0 ±4. 7） vs （48. 1 ±6. 1 ） ng/L] （both P = 0. 1300） and the number of CD4 ^＋ CD25^ ＋ Foxp3^ ＋ regulatory T cells increased in peripheral blood （8.0% ± 1.3% vs 5.1% ±2. 1%, P = 0

关 键 词：脂多糖 T淋巴细胞 调节性 哮喘 小鼠 

分 类 号：R562.25[医药卫生—呼吸系统]