Th2细胞因子调节哮喘炎症细胞转运机制的研究

Study on the regulation of Th2 cytokines in inflammatory cell traffic of asthma

目的 探讨Th2细胞因子IL-5、IL-13调节哮喘炎症过程中肺和骨髓之间的细胞转运机制。方法 建立哮喘动物模型,获取肺泡灌洗液,检测IL-5、IFN-γ,浓度并进行病理分析;应用原位杂交技术检测肺组织IL-5、IL-13 mRNA表达和骨髓IL-5mRNA表达;免疫组化法观察肺、骨髓IL-5免疫反应细胞;流式细胞仪检测骨髓CD34、CD3阳性细胞。结果 哮喘组肺泡灌洗液IL-5浓度明显高于对照组(P<0.001);哮喘组肺组织病理改变显示小气道痉挛,管壁周围炎性细胞浸润,以嗜酸粒细胞、淋巴细胞为主;哮喘组肺组织IL-5、IL-13 mRNA表达较对照组显著增加(P<0.01);哮喘组骨髓IL-5 mRNA阳性细胞明显增加(P<0.001),与肺组织IL-5 mRNA表达的增高密切相关(P<0.05);此外,哮喘组肺组织和骨髓IL-5免疫反应细胞显著增加(P<0.01),骨髓CD34、CD3细胞均显著增高(P<0.01),并且CD34增高与骨髓细胞表达IL-5 mRNA密切相关(P<0.05)。结论IL-5可能在转录和转录后水平均参与调节骨髓嗜酸粒细胞的功能和炎症细胞在肺和骨髓之间的转运。

Objective To explore the regulation of Th2 cytokines IL-5 , IL-13 in cell traffic between lung and bone marrow of asthma. Methods In asthmatic animal models bronchoalveolar lavage fluid (BALF) , IL-5, IFN-γ was detected and histological analysis was made, respectively. In situ hybridization was adopted to determine the status of IL-5, IL-13 mRNA in lung tissue and IL-5 mRNA in bone marrow. Irnmunohistochemistry methods were used to detect the status of IL-5 immunoreactive cells in lung tissue and bone marrow. The multiparameter flow-cytometric method was used to examine CD34 + and CD3 + progenitor cells in bone marrow. Results Compared with control group, the level of IL-5 in BALF was significantly increased in asthmatic group (P <0.001), Histological examination showed that infiltration of eosinophils and lymphocytes in the airway, accompanied by small airway spasm and increased production of mucus in asthmatic group. The overexpression of IL-5 , IL-13 mRNA was observed in asthmatic group (P <0.01) , and IL-5 mRNA in bone marrow of asthmatic group was increased (P <0.001) , which was correlated with the enhanced expression of IL-5 mRNA in the lung (P < 0. 05). IL-5 immunoreactive cells were increased in lung tissue and bone marrow in asthmatic group (P <0.01). CD34 and CD3 cells were clearly increased in bone marrow of asthmatic group (P < 0. 01). In addition, increase in the number of CD34 cells was associated with expression of IL-5 mRNA in bone marrow (P<0.05). Conclusion IL-5 may be involved in the regulation of eosinophils in bone marrow and cell traffic between lung and bone marrow of asthma on the level of transcription or after transcription.