Systemic deficiency of glutathione in cystic fibrosis

J. H. Roum, R. Buhl, N. G. McElvaney, Z. Borok, Ronald Crystal

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Abstract

Cystic fibrosis (CF), a disorder characterized by mutations of the CF transmembrane regulator gene, is characterized in the lung by chronic inflammation, leading to progressive damage to the airway epithelium, bronchiectasis, and chronic obstructive lung disease. One process contributing to the airway derangement is the chronic burden of oxidants released by inflammatory cells on the respiratory epithelial surface. With this background, we hypothesized that glutathione in respiratory epithelial lining fluid (ELF) in CF patients might be oxidized and/or diminished in amount compared with the in normal subjects. Recovery of ELF by bronchoalveolar lavage from young adults with CF (n = 21) and normal subjects (n = 25) demonstrated marked neutrophil-dominated inflammation in ELF in CF patients. As predicted, ELF in CF patients was characterized by a deficiency of glutathione (P < 0.001), but this was secondary to a reduction in reduced glutathione (P < 0.001), inasmuch as there were no differences in ELF levels of oxidized glutathione (P > 0.2). Unexpectedly, there was also a marked deficiency of reduced glutathione in plasma (P < 0.02); i.e., the glutathione 'deficiency' observed in ELF in CF patients is not limited to the site of the inflammation but is systemic. Although the etiology of this generalized deficiency of extracellular glutathione is unknown, it is important in considering options for treating the concomitant and devastating lung pathology in this disorder.

Original languageEnglish
Pages (from-to)2419-2424
Number of pages6
JournalJournal of Applied Physiology
Volume75
Issue number6
Publication statusPublished - 1 Dec 1993
Externally publishedYes

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Keywords

  • alveolar macrophage
  • bronchoscopy
  • lung epithelium
  • neutrophil
  • oxidants
  • reduced glutathione
  • respiratory epithelial lining fluid

ASJC Scopus subject areas

  • Endocrinology
  • Physiology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Roum, J. H., Buhl, R., McElvaney, N. G., Borok, Z., & Crystal, R. (1993). Systemic deficiency of glutathione in cystic fibrosis. Journal of Applied Physiology, 75(6), 2419-2424.