Département de médecine, Université Laval, Québec, Canada.
Hum Immunol. 2010 Feb;71(2):144-50. doi: 10.1016/j.humimm.2009.11.005. Epub 2009 Nov 12.
The implication of alveolar macrophages (AM) in asthma, a T(h)2 disease, has not been well characterized. Thus, the goal of this study is to better characterize AM phenotype of allergic asthmatic compared with normal subjects using genomic expression analyses. Microarray analyses were performed with AM isolated from bronchoalveolar lavage. Robust multiarray analysis (RMA) normalization and Smyth's moderated t test were used to select differentially expressed genes. Fifty differentially expressed genes were identified. Nineteen have been classified in categories linked to stress or immune responses and among them; nine are part of the heat shock protein (HSP) family. Difference of expression for three (HSPD1, PRNP, SERPINH1) of the five selected genes were validated using real-time reverse transcription-polymerase chain reaction. Enzyme-linked immunosorbent assay was used to measure the protein level of heat shock protein 60 (HSP60), the protein encoded by HSPD1, and showed difference in AM protein level between allergic asthmatic and control subjects. In summary, this study suggests that HSP gene family, particularly HSP60, is involved in AM functions in a context of allergic asthma. These results also support the involvement of AM immune functions in the development of an allergic asthmatic response.
肺泡巨噬细胞(AM)在哮喘(一种 Th2 疾病)中的作用尚未得到很好的描述。因此,本研究的目的是使用基因组表达分析,更好地描述过敏性哮喘患者的 AM 表型与正常受试者的 AM 表型。通过支气管肺泡灌洗分离 AM 进行微阵列分析。使用稳健多阵列分析(RMA)归一化和 Smyth 的适度 t 检验选择差异表达基因。鉴定出 50 个差异表达基因。其中 19 个被归类为与应激或免疫反应相关的类别,其中 9 个是热休克蛋白(HSP)家族的一部分。使用实时逆转录-聚合酶链反应(PCR)验证了 5 个选定基因中 3 个(HSPD1、PRNP 和 SERPINH1)的表达差异。酶联免疫吸附测定(ELISA)用于测量热休克蛋白 60(HSP60)的蛋白水平,该蛋白由 HSPD1 编码,并显示过敏性哮喘患者和对照组 AM 蛋白水平存在差异。总之,本研究表明 HSP 基因家族,特别是 HSP60,参与了过敏性哮喘情况下 AM 的功能。这些结果还支持 AM 免疫功能在过敏性哮喘反应发展中的作用。