22 research outputs found
Contribution by Polymorphonucleate Granulocytes to Elevated Gamma-Glutamyltransferase in Cystic Fibrosis Sputum
Background: Cystic fibrosis (CF) is an autosomal recessive disorder characterized by a chronic neutrophilic airways
inflammation, increasing levels of oxidative stress and reduced levels of antioxidants such as glutathione (GSH). Gammaglutamyltransferase
(GGT), an enzyme induced by oxidative stress and involved in the catabolism of GSH and its derivatives,
is increased in the airways of CF patients with inflammation, but the possible implications of its increase have not yet been
investigated in detail.
Principal Findings: The present study was aimed to evaluate the origin and the biochemical characteristics of the GGT
detectable in CF sputum. We found GGT activity both in neutrophils and in the fluid, the latter significantly correlating with
myeloperoxidase expression. In neutrophils, GGT was associated with intracellular granules. In the fluid, gel-filtration
chromatography showed the presence of two distinct GGT fractions, the first corresponding to the human plasma b-GGT
fraction, the other to the free enzyme. The same fractions were also observed in the supernatant of ionomycin and fMLPactivated
neutrophils. Western blot analysis confirmed the presence of a single band of GGT immunoreactive peptide in the
CF sputum samples and in isolated neutrophils.
Conclusions: In conclusion, our data indicate that neutrophils are able to transport and release GGT, thus increasing GGT
activity in CF sputum. The prompt release of GGT may have consequences on all GGT substrates, including major
inflammatory mediators such as S-nitrosoglutathione and leukotrienes, and could participate in early modulation of
inflammatory response