PT  - JOURNAL ARTICLE
AU  - C. Neurohr
AU  - A-G. Lenz
AU  - I. Ding
AU  - H. Leuchte
AU  - T. Kolbe
AU  - J. Behr
TI  - Glutamate-cysteine ligase modulatory subunit in BAL alveolar macrophages of healthy smokers
AID  - 10.1183/09031936.03.00080403
DP  - 2003 Jul 01
TA  - European Respiratory Journal
PG  - 82--87
VI  - 22
IP  - 1
4099  - http://erj.ersjournals.com/content/22/1/82.short
4100  - http://erj.ersjournals.com/content/22/1/82.full
SO  - Eur Respir J2003 Jul 01; 22
AB  - The antioxidant glutathione (GSH) is increased in the epithelial lining fluid (ELF) of chronic smokers. The rate-limiting enzyme in GSH synthesis is glutamate-cysteine ligase (GCL), also known as γ‐glutamylcysteine synthetase, consisting of a heavy, catalytic (GCLC) and a light, modulatory (GCLM) subunit. To determine the contribution of bronchoalveolar lavage (BAL) cells to GSH levels in ELF, BAL was performed in eight smokers and eight never-smokers. Intra- and extracellular total glutathione (GSHt) levels and GCL subunit expression were assessed. GSHt was increased in ELF from smokers (1,090.1±163.0 µM versus 559.2±48.2 µM). GSHt content of BAL cells (nmol·mg protein−1) was decreased in smokers without differences reaching statistical significance (8.0±1.4 versus 12.4±2.6). GCLM expression was also reduced in smokers (0.6±0.1 versus 2.8±0.4) and correlated with intracellular GSHt content. There was no significant difference in GCLC expression and in differential cell counts in BAL fluid. The authors conclude that smoking does increase glutathione levels in the epithelial lining fluid but not intracellular levels in bronchoalveolar lavage cells. The data suggest that the intracellular glutathione concentration of bronchoalveolar lavage cells (predominately alveolar macrophages) is regulated by the modulatory glutamate-cysteine ligase subunit rather than the catalytic subunit. J. Behr is supported by a grant from the Wilhelm-Sander-Stiftung, Germany.