This may be due both to an enormously pronounced lung inflammation in CF lungs, which leads to the continuous generation of free radicals by PMNs and consequently to profound oxidative protein damage and an insufficient protective effect of known antioxidants. Based on the correlation between the level of protein carbonyls, neutrophil granulocyte count, and lung function, the carbony-lation state of pulmonary proteins may be used as a marker of disease and help to explore pathophysiology of oxidative stress.
The pattern of the proteins that were carbonylated in the lavages was displayed by two-dimensional electrophoresis and Western blotting. The distribution of oxidized proteins on two-dimensional gels was different in the groups of patients with different carbonyl levels.
CF patients with low carbonyl content had fewer carbonylated protein spots on their gels. Furthermore, the overall degree of carbonyla-tion of individual, corresponding proteins was obviously less than that in patients with high carbonyl content. Interestingly, in addition to a broad range of serum proteins present in BALF, ie, albumine, Igs, and a1-antitrypsin, lung-specific proteins such as SP-A were heavily oxidized in CF patients. This directly showed oxidative modification of a protein essential for certain intra-alveolar functions, ie, the formation of tubular myelin and the resistance of surfactant to inhibition of its biophysical activity. read
Previously it has been shown that oxidation of SP-A also leads to changes in its function; and together with reported proteolytic damage and diminished levels of this protein in CF, additional oxidative changes may result in heavy impairment of SP-A-dependent immune function within the lung. Protein oxidation in the lungs of patients with CF may be assessed as protein carbonyls and may be a useful as marker of disease activity and oxidative lung damage. Because of the high level of oxidative stress present in the CF lung, its reduction is a valid therapeutic option. Whether or not a symptomatic-specific antioxidative therapy may be helpful has not been clarified, but it seems to be meaningful in the treatment of CF lung disease. However, clinical trials with natural and synthetic antioxidants must be performed. Until then, monitoring oxidative changes in CF airway secretions may give further insights into pathophysiology and help to define specific treatments. In summary, our results confirm the presence of increased oxidative stress in the lungs of patients with CF, even in subjects with normal lung function.