Morrison D, Strieter R M, Donnelly S C, Burdick M D, Kunkel S L, MacNee W
Dept of Medicine, University of Edinburgh, UK.
Eur Respir J. 1998 Nov;12(5):1067-72. doi: 10.1183/09031936.98.12051067.
Polymorphonuclear neutrophils (PMN) have been implicated in the pathogenesis of emphysema. The chemokines interleukin-8(IL-8), growth-related oncogene (GRO-alpha) and extractable nuclear antigen (ENA)-78 may be involved in the increased numbers of PMN in smokers' airspaces. The levels of these cytokines in bronchoalveolar lavage fluid (BALF) and bronchoalveolar lavage leukocyte conditioned medium (LCM), along with BALF PMN numbers in 12 smokers who abstained for 12 h (chronic smoking) or continued to smoke until I h before study (acute smoking) and seven nonsmokers were compared. Neutrophils in BALF increased in acute (1.96+/-0.53%, 0.99+/-0.32x10(6) cells) compared with chronic smokers (0.59+/-0.25%, 0.61+/-0.24x10(6) cells, p<0.05 nonsmokers) and nonsmokers (0.79+/-0.29%, 0.05+/-0.01x 10(6) cells, p<0.05). There were no differences in IL-8 or GRO-alpha in BALF between smokers and nonsmokers. ENA-78 levels were lower in smokers (p=0.006). There was no difference in IL-8, GRO-alpha or ENA-78 in LCM from unstimulated cells in smokers versus nonsmokers. After stimulation with lipopolysaccharide (LPS) 10 ng mL(-1), IL-8 release in acute smokers (p=0.04) and GRO-alpha release in smokers (p=0.009) were significantly higher than in nonsmokers. Following stimulation with LPS 100 ng.mL(-1), GRO-alpha release was higher in smokers (p=0.03) and increased further in acute smokers (p=0.02 versus nonsmokers, p=0.04 versus chronic smokers) and ENA-78 release increased in smokers (p=0.02 versus non-smokers). In conclusion, influx of polymorphonuclear neutrophils into smokers' airspaces is an acute phenomenon and neutrophil chemokine release from mixed bronchoalveolar lavage leukocytes is influenced by cigarette smoking and endotoxins.
多形核中性粒细胞（PMN）与肺气肿的发病机制有关。趋化因子白细胞介素-8（IL-8）、生长相关癌基因（GRO-α）和可提取核抗原（ENA）-78可能与吸烟者肺泡腔中PMN数量增加有关。比较了12名戒烟12小时（慢性吸烟）或在研究前1小时继续吸烟（急性吸烟）的吸烟者以及7名不吸烟者的支气管肺泡灌洗液（BALF）和支气管肺泡灌洗白细胞条件培养基（LCM）中这些细胞因子的水平，以及BALF中PMN的数量。与慢性吸烟者（0.59±0.25%，0.61±0.24×10⁶细胞，与不吸烟者相比p<0.05）和不吸烟者（0.79±0.29%，0.05±0.01×10⁶细胞，p<0.05）相比，急性吸烟者BALF中的中性粒细胞增加（1.96±0.53%，0.99±0.32×10⁶细胞）。吸烟者和不吸烟者BALF中的IL-8或GRO-α没有差异。吸烟者的ENA-78水平较低（p=0.006）。吸烟者和不吸烟者未受刺激细胞的LCM中IL-8、GRO-α或ENA-78没有差异。用10 ng/mL脂多糖（LPS）刺激后，急性吸烟者的IL-8释放（p=0.04）和吸烟者的GRO-α释放（p=0.009）显著高于不吸烟者。用100 ng/mL LPS刺激后，吸烟者的GRO-α释放较高（p=0.03），急性吸烟者进一步增加（与不吸烟者相比p=0.02，与慢性吸烟者相比p=0.04），吸烟者的ENA-78释放增加（与不吸烟者相比p=0.02）。总之，多形核中性粒细胞流入吸烟者的肺泡腔是一种急性现象，吸烟和内毒素会影响支气管肺泡灌洗混合白细胞中中性粒细胞趋化因子的释放。
