This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Day, B. J.
Right arrow Articles by Velsor, L. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Day, B. J.
Right arrow Articles by Velsor, L. W.

 Previous Article  |  Next Article 

Infection and Immunity, April 2004, p. 2045-2051, Vol. 72, No. 4
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.4.2045-2051.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Role for Cystic Fibrosis Transmembrane Conductance Regulator Protein in a Glutathione Response to Bronchopulmonary Pseudomonas Infection

Brian J. Day,1,2* Anna M. van Heeckeren,3 Elysia Min,1 and Leonard W. Velsor1

Department of Medicine, National Jewish Medical and Research Center,1 Departments of Medicine and Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver, Colorado,2 Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio3

Received 6 November 2003/ Returned for modification 2 December 2003/ Accepted 2 January 2004

The lung maintains an elevated level of glutathione (GSH) in epithelial lining fluid (ELF) compared to serum. The mechanism(s) by which the lung maintains high levels of ELF GSH and factors that modulate them are largely unexplored. We hypothesized that lung cystic fibrosis transmembrane conductance regulator protein (CFTR) modulates GSH efflux in response to extracellular stress, which occurs with lung infections. Mice were challenged intratracheally with Pseudomonas aeruginosa, and on the third day of infection bronchoalveolar lavage fluid was obtained and analyzed for cytokines and antioxidants. Lung tissue antioxidants and enzyme activities were also assessed. P. aeruginosa lung infection increased levels of inflammatory cytokines and neutrophils in the ELF. This corresponded with a marked threefold increase in GSH and a twofold increase in urate levels in the ELF of P. aeruginosa-infected wild-type mice. A twofold increase in urate levels was also observed among lung tissue antioxidants of P. aeruginosa-infected wild-type mice. There were no changes in markers of lung oxidative stress associated with the P. aeruginosa lung infection. In contrast with wild-type mice, the CFTR knockout mice lacked a significant increase in ELF GSH when challenged with P. aeruginosa, and this correlated with a decrease in the ratio of reduced to oxidized GSH in the ELF, a marker of oxidative stress. These data would suggest that the lung adapts to infectious agents with elevated ELF GSH and urate. Individuals with lung diseases associated with altered antioxidant transport, such as cystic fibrosis, might lack the ability to adapt to the infection and present with a more severe inflammatory response.

* Corresponding author. Mailing address: National Jewish Medical and Research Center, Goodman Building 715A, 1400 Jackson St., Denver, CO 80206. Phone: (303) 398-1121. Fax: (303) 270-2249. E-mail: dayb{at}njc.org.

Editor: F. C. Fang

Infection and Immunity, April 2004, p. 2045-2051, Vol. 72, No. 4
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.4.2045-2051.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Bergamini, G., Cigana, C., Sorio, C., Peruta, M. D., Pompella, A., Corti, A., Huaux, F. A., Leal, T., Assael, B. M., Melotti, P. (2009). Effects of Azithromycin on Glutathione S-Transferases in Cystic Fibrosis Airway Cells. Am. J. Respir. Cell Mol. Bio. 41: 199-206 [Abstract] [Full Text]  
  • Bartling, T. R., Drumm, M. L. (2009). Loss of CFTR results in reduction of histone deacetylase 2 in airway epithelial cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 297: L35-L43 [Abstract] [Full Text]  
  • Bradford, E. M., Sartor, M. A., Gawenis, L. R., Clarke, L. L., Shull, G. E. (2009). Reduced NHE3-mediated Na+ absorption increases survival and decreases the incidence of intestinal obstructions in cystic fibrosis mice. Am. J. Physiol. Gastrointest. Liver Physiol. 296: G886-G898 [Abstract] [Full Text]  
  • Bartling, T. R., Drumm, M. L. (2009). Oxidative Stress Causes IL8 Promoter Hyperacetylation in Cystic Fibrosis Airway Cell Models. Am. J. Respir. Cell Mol. Bio. 40: 58-65 [Abstract] [Full Text]  
  • Kariya, C., Chu, H. W., Huang, J., Leitner, H., Martin, R. J., Day, B. J. (2008). Mycoplasma pneumoniae Infection and Environmental Tobacco Smoke Inhibit Lung Glutathione Adaptive Responses and Increase Oxidative Stress. Infect. Immun. 76: 4455-4462 [Abstract] [Full Text]  
  • Lassen, N., Bateman, J. B., Estey, T., Kuszak, J. R., Nees, D. W., Piatigorsky, J., Duester, G., Day, B. J., Huang, J., Hines, L. M., Vasiliou, V. (2007). Multiple and Additive Functions of ALDH3A1 and ALDH1A1: CATARACT PHENOTYPE AND OCULAR OXIDATIVE DAMAGE IN Aldh3a1(-/-)/Aldh1a1(-/-) KNOCK-OUT MICE. J. Biol. Chem. 282: 25668-25676 [Abstract] [Full Text]  
  • Kariya, C., Leitner, H., Min, E., van Heeckeren, C., van Heeckeren, A., Day, B. J. (2007). A role for CFTR in the elevation of glutathione levels in the lung by oral glutathione administration. Am. J. Physiol. Lung Cell. Mol. Physiol. 292: L1590-L1597 [Abstract] [Full Text]  
  • Beharry, S., Ackerley, C., Corey, M., Kent, G., Heng, Y.-M., Christensen, H., Luk, C., Yantiss, R. K., Nasser, I. A., Zaman, M., Freedman, S. D., Durie, P. R. (2007). Long-term docosahexaenoic acid therapy in a congenic murine model of cystic fibrosis. Am. J. Physiol. Gastrointest. Liver Physiol. 292: G839-G848 [Abstract] [Full Text]  
  • Velsor, L. W., Kariya, C., Kachadourian, R., Day, B. J. (2006). Mitochondrial Oxidative Stress in the Lungs of Cystic Fibrosis Transmembrane Conductance Regulator Protein Mutant Mice. Am. J. Respir. Cell Mol. Bio. 35: 579-586 [Abstract] [Full Text]  
  • Starner, T. D., McCray, P. B. Jr. (2005). Pathogenesis of Early Lung Disease in Cystic Fibrosis: A Window of Opportunity To Eradicate Bacteria. ANN INTERN MED 143: 816-822 [Full Text]  
  • Baltes, N., N'diaye, M., Jacobsen, I. D., Maas, A., Buettner, F. F. R., Gerlach, G.-F. (2005). Deletion of the Anaerobic Regulator HlyX Causes Reduced Colonization and Persistence of Actinobacillus pleuropneumoniae in the Porcine Respiratory Tract. Infect. Immun. 73: 4614-4619 [Abstract] [Full Text]  
  • Day, B. J. (2005). Glutathione: A Radical Treatment for Cystic Fibrosis Lung Disease?. Chest 127: 12-14 [Full Text]  
  • Bishop, C., Hudson, V. M., Hilton, S. C., Wilde, C. (2005). A Pilot Study of the Effect of Inhaled Buffered Reduced Glutathione on the Clinical Status of Patients With Cystic Fibrosis. Chest 127: 308-317 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»