Proteomic profile of cystic fibrosis sputum cells in adults chronically infected with Pseudomonas aeruginosa

Lung disease is the main cause of morbidity and mortality in cystic fibrosis (CF) andinvolves chronic infection and perturbed immune responses. Tissue damage ismediated mostly by extracellular proteases, but other cellular proteins may alsocontribute to damage through their effect on cell activities and/or release into sputumfluid by means of active secretion or cell death.We employed Multidimensional Protein Identification Technology to identify sputumcellular proteins with consistently altered abundance in adults with CF, chronicallyinfected with Pseudomonas aeruginosa, compared to healthy controls. IngenuityPathway Analysis, Gene Ontology, protein abundance and correlation with lungfunction were used to infer their potential clinical significance.Differentially abundant proteins relate to Rho family small GTPase activity, immunecell movement/activation, generation of reactive oxygen species and dysregulation ofcell death and proliferation. Compositional breakdown identified high abundance ofproteins previously associated with neutrophil extracellular traps. Furthermore,negative correlations with lung function were detected for 17 proteins, many of whichhave previously been associated with lung injury.These findings expand current understanding of the mechanisms driving CF lungdisease and identify sputum cellular proteins with potential for use as indicators ofdisease status/prognosis, stratification determinants for treatment prescription or astherapeutic targets.