在急性呼吸应急综合征中中性粒细胞的全基因组转录概况
JatinderK Juss1, Jurgen Herre1, Malcolm Begg2
1University of Cambridge, Cambridge, UK.
Lancet (London, England)
|August 28, 2015
概括
急性呼吸困难综合征 (ARDS) 涉及中性粒细胞的炎症. 这项研究揭示了ARDS中性粒细胞的独特基因表达,为这种关键疾病提供了新的治疗点.
科学领域:
- 肺部医学
- 免疫学
- 基因组学
背景情况:
- 急性呼吸困难综合征 (ARDS) 的特征是中性粒细胞驱动的肺炎.
- 在ARDS患者中,多态核白细胞 (PMNs) 呈现出改变的激活,氧化突发和存活率.
- ARDS PMN 功能障碍的分子基础尚不完全理解.
研究的目的:
- 研究ARDS患者血液PMN的全基因组转录特征.
- 确定ARDSPMN功能和寿命的分子机制.
- 在ARDS中发现潜在的治疗目标来操纵PMN行为.
主要方法:
- 在ARDS患者 (n=10) 和健康对照者 (n=10) 的高纯度PMN上使用Affymetrix寡核酸阵列进行全球基因表达分析.
- 与实验室rhGM-CSF刺激的健康PMN进行比较.
- 使用Ingenuity路径分析软件进行路径分析.
主要成果:
- 与健康对照组相比,在ARDS PMN中表达的基因差异为1319.
- ARDS PMN基因表达特征与败血症和烧伤患者的数据集有很强的相关性.
- 在ARDS PMN中丰富的转录映射到参与癌症,细胞妥协,细胞亡和化学反应的途径.
结论:
- 这项研究提供了第一个高度纯净的ARDS血液PMN的全球基因组分析.
- ARDS PMN 具有显著的 de novo 转录活性,与之前观察到的异常功能和存活率相关.
- ARDS PMN 的转录学特征与败血症和烧伤非常相似,与 rhGM-CSF 刺激的 PMN 存在有限的重叠.
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