title: Susceptibility to COPD: differential proteomic profiling after acute smoking.
abstract: Cigarette smoking is the main risk factor for COPD (Chronic Obstructive Pulmonary Disease), yet only a subset of smokers develops COPD. Family members of patients with severe early-onset COPD have an increased risk to develop COPD and are therefore defined as "susceptible individuals". Here we perform unbiased analyses of proteomic profiles to assess how "susceptible individuals" differ from age-matched "non-susceptible individuals" in response to cigarette smoking. Epithelial lining fluid (ELF) was collected at baseline and 24 hours after smoking 3 cigarettes in young individuals susceptible or non-susceptible to develop COPD and older subjects with established COPD. Controls at baseline were older healthy smoking and non-smoking individuals. Five samples per group were pooled and analysed by stable isotope labelling (iTRAQ) in duplicate. Six proteins were selected and validated by ELISA or immunohistochemistry. After smoking, 23 proteins increased or decreased in young susceptible individuals, 7 in young non-susceptible individuals, and 13 in COPD in the first experiment; 23 proteins increased or decreased in young susceptible individuals, 32 in young non-susceptible individuals, and 11 in COPD in the second experiment. SerpinB3 and Uteroglobin decreased after acute smoke exposure in young non-susceptible individuals exclusively, whereas Peroxiredoxin I, S100A9, S100A8, ALDH3A1 (Aldehyde dehydrogenase 3A1) decreased both in young susceptible and non-susceptible individuals, changes being significantly different between groups for Uteroglobin with iTRAQ and for Serpin B3 with iTRAQ and ELISA measures. Peroxiredoxin I, SerpinB3 and ALDH3A1 increased in COPD patients after smoking. We conclude that smoking induces a differential protein response in ELF of susceptible and non-susceptible young individuals, which differs from patients with established COPD. This is the first study applying unbiased proteomic profiling to unravel the underlying mechanisms that induce COPD. Our data suggest that SerpinB3 and Uteroglobin could be interesting proteins in understanding the processes leading to COPD.
authors.affiliation: University of Groningen, Department of Pharmacy, Analytical Biochemistry, Groningen, The Netherlands.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Franciosi
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Pulmonary Diseases, Groningen Research Institute of Asthma and COPD (GRIAC), Groningen, The Netherlands.
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Pulmonary Diseases, Groningen Research Institute of Asthma and COPD (GRIAC), Groningen, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Berge
authors.affiliation: University of Groningen, Department of Pharmacy, Analytical Biochemistry, Groningen, The Netherlands.
authors.forename: Natalia
authors.initials: N
authors.lastname: Govorukhina
authors.affiliation: University of Groningen, Department of Pharmacy, Analytical Biochemistry, Groningen, The Netherlands.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Horvatovich
authors.affiliation: Department of Biochemistry, University of Groningen, Netherlands Proteomics Centre, Groningen, The Netherlands.
authors.forename: Fabrizia
authors.initials: F
authors.lastname: Fusetti
authors.affiliation: Department of Biochemistry, University of Groningen, Netherlands Proteomics Centre, Groningen, The Netherlands.
authors.forename: Bert
authors.initials: B
authors.lastname: Poolman
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Pathology, Groningen Research Institute of Asthma and COPD (GRIAC), Groningen, The Netherlands.
authors.forename: Monique E
authors.initials: ME
authors.lastname: Lodewijk
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Pathology, Groningen Research Institute of Asthma and COPD (GRIAC), Groningen, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Timens
authors.affiliation: University of Groningen, Department of Pharmacy, Analytical Biochemistry, Groningen, The Netherlands.
authors.forename: Rainer
authors.initials: R
authors.lastname: Bischoff
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Pulmonary Diseases, Groningen Research Institute of Asthma and COPD (GRIAC), Groningen, The Netherlands.
authors.forename: Nick H T
authors.initials: NH
authors.lastname: ten Hacken
mesh_terms: D000293:Adolescent; D000328:Adult; D004198:Disease Susceptibility; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D040901:Proteomics; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology* / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors; D055815:Young Adult