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

Authors

  • KRISTIN BLIDBERG,

    Corresponding author
    1. Lung and Allergy Research, The National Institute of Environmental Medicine, Karolinska Institutet
      Kristin Blidberg, Lung and Allergy Research, National Institute of Environmental Medicine, Karolinska Institutet, Box 287, SE-171 77 Stockholm, Sweden. Email: kristin.blidberg@ki.se
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  • LENA PALMBERG,

    1. Lung and Allergy Research, The National Institute of Environmental Medicine, Karolinska Institutet
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  • BARBRO DAHLÉN,

    1. Division of Respiratory Medicine and Allergy, Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden
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  • ANN-SOFIE LANTZ,

    1. Division of Respiratory Medicine and Allergy, Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden
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  • KJELL LARSSON

    1. Lung and Allergy Research, The National Institute of Environmental Medicine, Karolinska Institutet
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  • Conflict of interest statement: This study was supported by grants from the Swedish Heart and Lung Foundation, Karolinska Institutet, AstraZeneca Sweden, Swedish Medical Research Council, King Gustaf V's and Queen Victoria's Foundation and Stockholm City County.

  • Kjell Larsson has, during the last five years, on one or more occasions served on an advisory board and/or served as speaker and/or participated in education arranged by AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, MSD, Nycomed, Novartis and Pfizer. Kjell Larsson has also, during the last five years, received unrestricted research grants from Boehringer Ingelheim, GlaxoSmithKline and AstraZeneca.

Kristin Blidberg, Lung and Allergy Research, National Institute of Environmental Medicine, Karolinska Institutet, Box 287, SE-171 77 Stockholm, Sweden. Email: kristin.blidberg@ki.se

ABSTRACT

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-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 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-α 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-α and chemotactic response suggests that TNF-α is involved in neutrophil activation, resulting in enhanced migration.

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