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Glutamate-cysteine ligase modulatory subunit in BAL alveolar macrophages of healthy smokers

¹ Dept of Internal Medicine, Division for Pulmonary Diseases, Klinikum Grosshadern, Ludwig-Maximilians-Universitiy of Munich, Munich and ² National Research Centre for Environment and Health (GSF), Institute for Inhalation Biology, Neuherberg, Germany

CORRESPONDENCE: J. Behr, Dept of Internal Medicine I, Division for Pulmonary Diseases, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, 81377 Munich, Germany. Fax: 49 8970958877. E-mail: jbehr@med1.med.uni-muenchen.de

Keywords: alveolar macrophages, bronchoalveolar lavage, glutamate-cysteine ligase, glutathione, smoker

Received: August 30, 2002
Accepted January 5, 2003

J. Behr is supported by a grant from the Wilhelm-Sander-Stiftung, Germany.

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 -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 (GSH_t) levels and GCL subunit expression were assessed.

GSH_t was increased in ELF from smokers (1,090.1±163.0 µM versus 559.2±48.2 µM). GSH_t 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 GSH_t 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.

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