title: Contribution by polymorphonucleate granulocytes to elevated gamma-glutamyltransferase in cystic fibrosis sputum.
abstract: 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). Gamma-glutamyltransferase (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.
  
  
  RESULTS
  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 fMLP-activated 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.
authors.affiliation: Dipartimento di Patologia Sperimentale, Università di Pisa, Scuola Medica, Pisa, Italy. alessandro.corti@med.unipi.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Corti
authors.forename: Maria
authors.initials: M
authors.lastname: Franzini
authors.forename: Silvana
authors.initials: S
authors.lastname: Cianchetti
authors.forename: Gabriella
authors.initials: G
authors.lastname: Bergamini
authors.forename: Evelina
authors.initials: E
authors.lastname: Lorenzini
authors.forename: Paola
authors.initials: P
authors.lastname: Melotti
authors.forename: Aldo
authors.initials: A
authors.lastname: Paolicchi
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Paggiaro
authors.forename: Alfonso
authors.initials: A
authors.lastname: Pompella
mesh_terms: D000293:Adolescent; D000328:Adult; D061207:Calcium Ionophores / Q000494:pharmacology; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000201:enzymology*; D005260:Female; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000201:enzymology*; D009195:Peroxidase / Q000032:analysis; D013183:Sputum / Q000201:enzymology*; D055815:Young Adult; D005723:gamma-Glutamyltransferase / Q000032:analysis / Q000378:metabolism*
chemical_list: D061207:Calcium Ionophores; D015759:Ionomycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009195:Peroxidase; D005723:gamma-Glutamyltransferase; C554782:gamma-glutamyltransferase, human