Lung and Allergy Research, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Respirology. 2012 Jul;17(5):854-60. doi: 10.1111/j.1440-1843.2012.02181.x.
The number of airway neutrophils is increased in chronic obstructive pulmonary disease (COPD), and this may have a central pathophysiological role in the disease. In addition, activation of neutrophils increases their migration into sites of injury. We hypothesize that circulating neutrophils are activated in smokers.
Peripheral blood neutrophils were isolated from healthy non-smokers (n = 15), and smokers with (n = 15) or without COPD (n = 15), who were matched with regard to cumulative tobacco exposure, and chemotactic responses to N-formyl-methionyl-leucyl-phenylalanine (fMLP), interleukin-8 (IL-8, CXCL8) and leukotriene B(4) (LTB(4)) were assessed using the ChemoTx System (Neuro Probe Inc., Gaithersburg, MD, USA). Serum tumour necrosis factor-α (TNF-α) concentrations were measured by ELISA. Surface expression of the neutrophil activation marker, CD11b, was measured by flow cytometry.
The chemotactic response to CXCL8 was increased in smokers with or without COPD (P < 0.05). Migration towards LTB(4) was increased in smokers without COPD compared with non-smokers (P < 0.05), whereas there was no difference in fMLP-induced chemotaxis between the groups. There was a correlation between serum TNF-α levels and migration induced by IL-8 (Rho = 0.442; P = 0.038) and LTB(4) (Rho = 0.428; P = 0.044) in the smokers. Furthermore, there was a tendency towards higher CD11b expression in the COPD group (P = 0.057).
Chemotaxis of circulating neutrophils towards CXCL8, and partly towards LTB(4), is increased in smokers, indicating a systemic influence of smoking on cell activation, irrespective of the presence of airflow limitation. The relationship between TNF-α and chemotactic response suggests that TNF-α is involved in neutrophil activation, resulting in enhanced migration.
慢性阻塞性肺疾病（COPD）患者气道中的中性粒细胞数量增加，这可能在疾病的发病机制中发挥核心作用。此外，中性粒细胞的激活会增加其向损伤部位的迁移。我们假设吸烟会使循环中的中性粒细胞激活。
从健康不吸烟者（n = 15）、有（n = 15）或无 COPD（n = 15）的吸烟者中分离外周血中性粒细胞，这些吸烟者的吸烟量与无 COPD 的吸烟者相匹配，并使用 ChemoTx 系统（Neuro Probe Inc.，Gaithersburg，MD，USA）评估其对 N-甲酰基-甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）、白细胞介素-8（IL-8，CXCL8）和白三烯 B4（LTB4）的趋化反应。通过 ELISA 测定血清肿瘤坏死因子-α（TNF-α）浓度。通过流式细胞术测定中性粒细胞活化标志物 CD11b 的表面表达。
有或无 COPD 的吸烟者对 CXCL8 的趋化反应增加（P < 0.05）。与不吸烟者相比，无 COPD 的吸烟者对 LTB4 的迁移增加（P < 0.05），而各组 fMLP 诱导的趋化作用无差异。吸烟者中血清 TNF-α水平与 IL-8（Rho = 0.442；P = 0.038）和 LTB4（Rho = 0.428；P = 0.044）诱导的迁移之间存在相关性。此外，COPD 组的 CD11b 表达有升高趋势（P = 0.057）。
吸烟使循环中性粒细胞向 CXCL8 和部分向 LTB4 的趋化性增加，表明吸烟对细胞激活具有全身性影响，而与气流受限的存在无关。TNF-α 与趋化反应之间的关系表明 TNF-α参与中性粒细胞的激活，导致迁移增加。
