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 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.

RESULTS

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).

CONCLUSIONS

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.