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

Respirology. 2012 Jul;17(5):854-60. doi: 10.1111/j.1440-1843.2012.02181.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Case-Control Studies
  • Cell Movement / physiology*
  • Chemotaxis, Leukocyte / drug effects
  • Female
  • Humans
  • Interleukin-8 / pharmacology
  • Leukotriene B4 / pharmacology
  • Male
  • Middle Aged
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils / pathology*
  • Neutrophils / physiology*
  • Pulmonary Disease, Chronic Obstructive / blood
  • Pulmonary Disease, Chronic Obstructive / pathology*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Smoking*
  • Tumor Necrosis Factor-alpha / blood


  • Interleukin-8
  • Tumor Necrosis Factor-alpha
  • Leukotriene B4
  • N-Formylmethionine Leucyl-Phenylalanine