Armstrong J, Sargent C, Singh D
University of Manchester, NIHR Translational Research Facility, University Hospital of South Manchester Foundation Trust, Manchester, UK.
Clin Exp Immunol. 2009 Oct;158(1):74-83. doi: 10.1111/j.1365-2249.2009.03986.x.
It has been reported that alveolar macrophages from patients with chronic obstructive pulmonary disease (COPD) display glucocorticoid (Gc) resistance. The Gc sensitivity of inflammatory mediators released by COPD macrophages may vary. The objective of this study was to identify Gc-insensitive inflammatory mediators produced by lipopolysaccharide (LPS)-stimulated alveolar macrophages from COPD patients. LPS-stimulated alveolar macrophages from 15 COPD patients, nine smokers (S) and nine healthy non-smokers (HNS) were stimulated with LPS with or without dexamethasone (100 and 1000 nM). Luminex and enzyme-linked immunosorbent assay were used to measure 23 inflammatory mediators. After LPS stimulation there were lower levels of inflammatory mediators in COPD patients and S compared to HNS. There was no difference between groups for the effects of dexamethasone at either concentration (P > 0.05 for all comparisons). Tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and growth-related oncogene (GRO)-alpha displayed the greatest sensitivity to dexamethasone in COPD patients, while IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) were the least sensitive. COPD macrophages have a reduced response to LPS. Gc sensitivity was similar in COPD macrophages compared to controls. We identify some Gc-insensitive cytokines, including GM-CSF, G-CSF and IL-8, that may be involved in the progression of airway inflammation in COPD patients.
据报道，慢性阻塞性肺疾病（COPD）患者的肺泡巨噬细胞表现出糖皮质激素（Gc）抵抗。COPD巨噬细胞释放的炎症介质对Gc的敏感性可能有所不同。本研究的目的是鉴定由脂多糖（LPS）刺激的COPD患者肺泡巨噬细胞产生的对Gc不敏感的炎症介质。来自15名COPD患者、9名吸烟者（S）和9名健康非吸烟者（HNS）的LPS刺激的肺泡巨噬细胞，在有或没有地塞米松（100和1000 nM）的情况下用LPS刺激。使用Luminex和酶联免疫吸附测定法测量23种炎症介质。LPS刺激后，与HNS相比，COPD患者和S中的炎症介质水平较低。两种浓度的地塞米松对各组的影响没有差异（所有比较的P>0.05）。肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6和生长相关癌基因（GRO）-α在COPD患者中对地塞米松表现出最大的敏感性，而IL-8、粒细胞-巨噬细胞集落刺激因子（GM-CSF）和粒细胞集落刺激因子（G-CSF）最不敏感。COPD巨噬细胞对LPS的反应降低。与对照组相比，COPD巨噬细胞中的Gc敏感性相似。我们鉴定出一些对Gc不敏感的细胞因子，包括GM-CSF、G-CSF和IL-8，它们可能参与COPD患者气道炎症的进展。
