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Chronic obstructive pulmonary disease
Enhanced pulmonary leptin expression in patients with severe COPD and asymptomatic smokers
  1. J H J Vernooy1,2,
  2. N E A Drummen1,2,
  3. R J van Suylen3,
  4. R H E Cloots2,4,
  5. G M Möller5,
  6. K R Bracke6,
  7. S Zuyderduyn5,
  8. M A Dentener1,2,
  9. G G Brusselle6,
  10. P S Hiemstra5,
  11. E F M Wouters1,2,7
  1. 1
    Department of Respiratory Medicine, University Hospital Maastricht, Maastricht, The Netherlands
  2. 2
    Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands
  3. 3
    Department of Pathology, University Hospital Maastricht, Maastricht, The Netherlands
  4. 4
    Department of Anatomy & Embryology, Maastricht University, Maastricht, The Netherlands
  5. 5
    Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands
  6. 6
    Department of Respiratory Diseases, University Hospital Ghent, Ghent, Belgium
  7. 7
    CIRO Horn, Horn, The Netherlands
  1. Dr J H J Vernooy, Department of Respiratory Medicine, University Hospital Maastricht, P O Box 5800, 6202 AZ Maastricht, The Netherlands; j.vernooy{at}pul.unimaas.nl

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is characterised by an abnormal inflammatory reaction of the lungs involving activation of epithelial cells. Leptin is a pleiotropic cytokine important in the regulation of immune responses via its functional receptor Ob-Rb. This study was undertaken to test the hypothesis that severe COPD is associated with increased leptin expression in epithelial cells.

Methods: Immunohistochemistry for leptin was performed on peripheral lung specimens from 20 patients with COPD (GOLD stage 4), 14 asymptomatic ex-smokers and 13 never smokers. Leptin and Ob-Rb mRNA expression were determined by rtPCR in cultured primary bronchial epithelial cells and primary type II pneumocytes. NCI-H292 and A549 cell lines were used to study functional activation of leptin signalling.

Results: Leptin immunoreactivity in lung tissue was observed in bronchial epithelial cells, type II pneumocytes, macrophages (tissue/alveolar) and interstitial lymphocytic infiltrates. rtPCR analysis confirmed pulmonary leptin and Ob-Rb mRNA expression in primary bronchial epithelial cells and pneumocytes. Leptin-expressing bronchial epithelial cells and alveolar macrophages were markedly higher in patients with severe COPD and ex-smokers than in never smokers (p<0.02). Exposure of cultured primary bronchial epithelial cells to smoke resulted in increased expression of both leptin and Ob-Rb (p<0.05). Leptin induced phosphorylation of STAT3 in both NCI-H292 and A549 cells.

Conclusions: Leptin expression is increased in bronchial epithelial cells and alveolar macrophages of ex-smokers with or without severe COPD compared with never smokers. A functional leptin signalling pathway is present in lung epithelial cells.

https://doi.org/10.1136/thx.2007.085423

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    Footnotes

    • ▸ Additional details are published online only at http://thorax.bmj.com/content/vol64/issue1

    • Funding: This study was supported by research grants of the Netherlands Asthma Foundation (3.2.05.046), Concerted Research Action of the University of Ghent (BOF/GOA 01251504) and AstraZeneca, The Netherlands.

    • Competing interests: None.

    • Ethics approval: The study was approved by the medical ethical committees of the University Hospital in Maastricht, Ghent and Leuven. All subjects gave written informed consent.