CF sputum LC-MSMS - Proteomic profile of cystic fibrosis sputum cells in adults chronically infected with Pseudomonas aeruginosa

ABSTRACT: Lung disease is the main cause of morbidity and mortality in cystic fibrosis (CF), and involves chronic infection by a destructive microbiota and perturbed innate and adaptive immune responses. Tissue damage is considered to be mediated mostly by proteases, but other bacterial and host factors may also play a role. To determine the presence of potentially injurious proteins we employed semi-quantitative Multidimensional Protein Identification Technology to identify sputum cellular proteins with consistently altered expression in CF compared to healthy controls. Ingenuity Pathway Analysis, Gene Ontology functions, protein abundance and correlation with lung function were used to infer their clinical significance. The CF proteome exhibited differential expression of proteins relating to Rho family small GTPase activity, immune cell movement and activation, generation of reactive oxygen species and dysregulation of cell death and proliferation. Compositional breakdown established neutrophil extracellular trap proteins as the consistently most abundant cellular proteins detected, while a further 13 biologically relevant proteins were found to correlate negatively with lung function. These findings expand the current understanding of the mechanisms underlying CF lung disease and identify sputum cell proteins which might be useful as markers of disease status, prognostic indicators, stratification determinants for treatment prescription or as therapeutic targets.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Erythrocyte, Platelet, B Cell, T Cell, Leukocyte, Dendritic Cell, Sputum, Epithelial Cell, Neutrophil, Fibroblast, Macrophage

DISEASE(S): Cystic Fibrosis

SUBMITTER: S Pattison  

LAB HEAD: Joseph Stuart Elborn

PROVIDER: PXD001985 | Pride | 2017-05-19

REPOSITORIES: Pride