Enhanced pulmonary leptin expression in patients with severe COPD and asymptomatic smokers.
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.
Department of Respiratory Medicine, University Hospital Maastricht, Maastricht, The Netherlands. j.vernooy@pul.unimaas.nl
J H J
JH
Vernooy
N E A
NE
Drummen
R J
RJ
van Suylen
R H E
RH
Cloots
G M
GM
Möller
K R
KR
Bracke
S
S
Zuyderduyn
M A
MA
Dentener
G G
GG
Brusselle
P S
PS
Hiemstra
E F M
EF
Wouters
D015153:Blotting, Western; D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D020738:Leptin / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D054411:Receptors, Leptin / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism*; D014797:Vital Capacity / Q000502:physiology
D020738:Leptin; D012333:RNA, Messenger; D054411:Receptors, Leptin