Am. J. Respir. Crit. Care Med., Vol 153, No. 2, Feb 1996, 742-746.
Glutathione depletion in epithelial lining fluid of lung allograft patients
MA Baz, VF Tapson, VL Roggli, P Van Trigt and CA Piantadosi
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
The lower respiratory tract is protected against reactive oxygen species
(ROS) by a complex antioxidant system. In the epithelial lining fluid
(ELF), glutathione (L-alpha-glutamyl-L-cysteinylglycine, GSH) is essential
for adequate protection of pneumocytes from potential toxicity mediated by
extracellular hydrogen peroxide (H2O2). We assessed the concentration of
total GSH in bronchoalveolar lavage fluid (BALF) in lung allograft patients
in the absence and presence of acute rejection. Bronchoalveolar lavage
(BAL) and biopsies were performed concurrently on 36 occasions in 17
patients who had undergone lung transplantation. BALF samples were divided
into two groups on the basis of presence or absence of acute lung rejection
on transbronchial biopsy. Seven BALF samples were obtained from control
subjects for comparison. The BALF data demonstrated significantly
lymphocyte recruitment and evidence of lung injury during acute rejection
episodes. Transplant allografts without rejection showed significant
depletion of total GSH in the ELF as compared with that of normal
volunteers (94.0 +/- 9.7 microM versus 302.6 +/- 40.8 microM, p < 0.01).
Transplant allografts with acute rejection had a slightly higher GSH
concentration in their ELF (179.8 +/- 34.7), but this was still lower than
control values. The deficiency of total GSH in the alveolar fluid may
predispose lung allografts to extracellular H2O2-mediated toxicity.