Increased neutrophil migration in smokers with or without chronic obstructive pulmonary disease

Background and objective: 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. Methods: 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 B4 (LTB4) were assessed using the ChemoTx System (Neuro Probe Inc., Gaithersburg, MD, USA). Serum tumour necrosis factor-a (TNF-a) concentrations were measured by ELISA. Surface expression of the neutrophil activation marker, CD11b, was measured by flow cytometry. Results: The chemotactic response to CXCL8 was increased in smokers with or without COPD (P < 0.05). Migration towards LTB4 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-a levels and migration induced by IL-8 (Rho = 0.442; P = 0.038) and LTB4 (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). Conclusions: Chemotaxis of circulating neutrophils towards CXCL8, and partly towards LTB4, is increased in smokers, indicating a systemic influence of smoking on cell activation, irrespective of the presence of airflow limitation. The relationship between TNF-a and chemotactic response suggests that TNF-a is involved in neutrophil activation, resulting in enhanced migration.