title: Granule cytotoxic activity and oxidative DNA damage in smoking and nonsmoking patients with asthma.
abstract: BACKGROUND
  Lung cytotoxic mechanisms trigger the release of perforin and granzymes, causing oxidative DNA damage that ultimately leads to apoptosis. These effects, although demonstrated in COPD, have not been investigated in patients with asthma and in particular in patients with asthma who smoke. Our aim was to measure perforin, granzyme A, granzyme B, and 8-OHdG expression in sputum from smoking and nonsmoking patients with asthma, compared with smoking and nonsmoking control subjects.
  
  
  METHODS
  Perforin, granzyme A, granzyme B, and 8-OHdG expression levels were detected by enzyme-linked immunosorbent assays in induced sputum specimens.
  
  
  RESULTS
  Perforin expression was increased in 40% of smokers and 45% of smoking patients with asthma and in only 7% of nonsmoking patients with asthma (P = .004), compared with control subjects' values. In contrast, granzymes A and B levels were increased in &gt; 40% of patients in all three groups vs control subjects. Finally, 8-OHdG levels were elevated in 35% of smoking patients with asthma, in 20% of smokers, and in only 10% of nonsmoking patients with asthma. Statistical analysis revealed a positive correlation between granzyme A (P &lt; .001) and granzyme B (P = .006) expression levels and the number of pack-years in smoking patients with asthma.
  
  
  CONCLUSIONS
  Asthma cytotoxic immune response is mainly represented by granzymes A and B, whereas in smoking patients with asthma perforin and 8-OHdG are additionally involved, resembling the immune response in COPD.
authors.affiliation: Department of Thoracic Medicine, University Hospital of Heraklion, Medical School, University of Crete, Heraklion, Crete.
authors.forename: Athanasia
authors.initials: A
authors.lastname: Proklou
authors.affiliation: Laboratory of Molecular and Cellular Pulmonology, Medical School, University of Crete, Heraklion, Crete.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Soulitzis
authors.affiliation: Laboratory of Molecular and Cellular Pulmonology, Medical School, University of Crete, Heraklion, Crete.
authors.forename: Eirini
authors.initials: E
authors.lastname: Neofytou
authors.affiliation: First University Department of Respiratory Medicine, Chest Diseases Hospital "Sotiria", Athens, Greece.
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Rovina
authors.affiliation: Seventh Respiratory Medicine Department and Asthma Center, Chest Diseases Hospital "Sotiria", Athens, Greece.
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Zervas
authors.affiliation: Seventh Respiratory Medicine Department and Asthma Center, Chest Diseases Hospital "Sotiria", Athens, Greece.
authors.forename: Mina
authors.initials: M
authors.lastname: Gaga
authors.affiliation: Department of Thoracic Medicine, University Hospital of Heraklion, Medical School, University of Crete, Heraklion, Crete; Laboratory of Molecular and Cellular Pulmonology, Medical School, University of Crete, Heraklion, Crete.
authors.forename: Nikolaos M
authors.initials: NM
authors.lastname: Siafakas
authors.affiliation: Department of Thoracic Medicine, University Hospital of Heraklion, Medical School, University of Crete, Heraklion, Crete; Laboratory of Molecular and Cellular Pulmonology, Medical School, University of Crete, Heraklion, Crete. Electronic address: tzortzaki@med.uoc.gr.
authors.forename: Eleni G
authors.initials: EG
authors.lastname: Tzortzaki
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D001249:Asthma / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D005260:Female; D053804:Granzymes / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D054353:Perforin / Q000096:biosynthesis*; D012907:Smoking / Q000378:metabolism*
chemical_list: D054353:Perforin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D053804:Granzymes; D003849:Deoxyguanosine