Mattson Jeanine D, Haus Brian M, Desai Bela, Ott Wayne, Basham Beth, Agrawal Madhuri, Ding Wei, Hildemann Lynn M, Abitorabi Karin M, Canfield James, Mak Gordon, Guvenc-Tuncturk Sebnem, Malefyt Rene de Waal, McClanahan Terrill K, Fick Robert B, Kuschner Ware G
Department of Experimental Pathology and Pharmacology, Schering-Plough Biopharma, Palo Alto, California, USA.
Exp Lung Res. 2008 Dec;34(10):631-62. doi: 10.1080/01902140802322256.
Chronic obstructive pulmonary diseases (COPD) may increase air pollution-related mortality. The relationship of immune mechanisms to mortality caused by fine particulates in healthy and COPD populations is incompletely understood. The objective of this study was to determine whether fine particulates from a single biomass fuel alter stress and inflammation biomarkers in people with COPD. Healthy and COPD subjects were exposed to smoke in a controlled indoor setting. Immune responses were quantified by measuring cell surface marker expression with flow-cytometric analysis and mRNA levels with quantitative reverse transcriptase-polymerase chain reactions in whole blood before and after exposure. Preexposure COPD subjects had more leukocytes, mainly CD14(+) monocytes and neutrophils, but fewer CD3(+) T cells. Fifty-seven of 186 genes were differentially expressed between healthy and COPD subjects' peripheral blood mononuclear cells (PBMCs). Of these, only nuclear factor (NF)-kappa B1, TIMP-1, TIMP-2, and Duffy genes were up-regulated in COPD subjects. At 4 hours post smoke exposure, monocyte levels decreased only in healthy subjects. Fifteen genes, particular to inflammation, immune response, and cell-to-cell signaling, were differentially expressed in COPD subjects, versus 4 genes in healthy subjects. The authors observed significant differences in subjects' PBMCs, which may elucidate the adverse effects of air pollution particulates on people with COPD.
慢性阻塞性肺疾病（COPD）可能会增加与空气污染相关的死亡率。免疫机制与健康人群和COPD人群中细颗粒物所致死亡率之间的关系尚未完全明确。本研究的目的是确定单一生物质燃料产生的细颗粒物是否会改变COPD患者的应激和炎症生物标志物。健康受试者和COPD患者在可控的室内环境中接触烟雾。通过流式细胞术分析测量细胞表面标志物表达以及用定量逆转录聚合酶链反应测量全血暴露前后的mRNA水平来量化免疫反应。暴露前，COPD患者的白细胞更多，主要是CD14(+)单核细胞和中性粒细胞，但CD3(+)T细胞较少。186个基因中有57个在健康受试者和COPD患者的外周血单核细胞（PBMC）中差异表达。其中，只有核因子（NF）-κB1、TIMP-1、TIMP-2和达菲基因在COPD患者中上调。烟雾暴露4小时后，单核细胞水平仅在健康受试者中下降。15个与炎症、免疫反应和细胞间信号传导相关的基因在COPD患者中差异表达，而在健康受试者中为4个。作者观察到受试者PBMC存在显著差异，这可能阐明空气污染颗粒物对COPD患者的不利影响。
