Enhanced pulmonary leptin expression in patients with severe COPD and asymptomatic smokers.

J.H. Vernooy*, N.E. Drummen, R.J. van Suylen, R.H. Cloots, G.M. Moller, K.R. Bracke, S. Zuyderduyn, M.A. Dentener, G.G. Brusselle, P.S. Hiemstra, E.F. Wouters

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review


    BACKGROUND: COPD is characterized 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 COPD patients (GOLD 4), 14 asymptomatic (ex-)smokers and 13 never smokers. Leptin and Ob-Rb mRNA expression was determined by rtPCR in cultured primary bronchial epithelial cells (BEC) 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 BEC, type II pneumocytes, macrophages (tissue/alveolar), and interstitial lymphocytic infiltrates. rtPCR analysis confirmed pulmonary leptin and Ob-Rb mRNA expression in primary BEC and pneumocytes. Leptin-expressing BEC and alveolar macrophages were markedly higher in severe COPD patients and (ex-) smokers versus never smokers (p<0.02). Exposure of cultured primary BEC 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 BEC and alveolar macrophages of (ex-) smokers with or without severe COPD versus never smokers. A functional leptin signalling pathway is present in lung epithelial cells.
    Original languageEnglish
    Pages (from-to)26-32
    Issue number1
    Publication statusPublished - 1 Jan 2009

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