Abstract
Lung disease is the main cause of morbidity and mortality in cystic fibrosis (CF), and involves chronic infection and perturbed immune responses. Tissue damage is mediated mostly by extracellular proteases, but other cellular proteins may also contribute to damage through their effect on cell activities and/or release into sputum fluid by means of active secretion or cell death.
We employed MudPIT (multidimensional protein identification technology) to identify sputum cellular proteins with consistently altered abundance in adults with CF, chronically infected with Pseudomonas aeruginosa, compared with healthy controls. Ingenuity Pathway Analysis, Gene Ontology, protein abundance and correlation with lung function were used to infer their potential clinical significance.
Differentially abundant proteins relate to Rho family small GTPase activity, immune cell movement/activation, generation of reactive oxygen species, and dysregulation of cell death and proliferation. Compositional breakdown identified high abundance of proteins previously associated with neutrophil extracellular traps. Furthermore, negative correlations with lung function were detected for 17 proteins, many of which have previously been associated with lung injury.
These findings expand our current understanding of the mechanisms driving CF lung disease and identify sputum cellular proteins with potential for use as indicators of disease status/prognosis, stratification determinants for treatment prescription or therapeutic targets.
Abstract
CF sputum proteomics detects high abundance of NET proteins and identifies proteins correlating negatively with FEV1 http://ow.ly/hnX830aEPki
Footnotes
This article has supplementary material available from erj.ersjournals.com
Support statement: S.H. Pattison was funded by the Cystic Fibrosis Trust Project Grant PJ545. D.J. Pappin, S. Peacock and the proteomics work were part supported by the National Institutes of Health/National Cancer Institute Cancer Center Support Grant 5P30CA045508. Funding information for this article has been deposited with the Crossref Funder Registry.
Conflict of interest: None declared.
- Received August 5, 2016.
- Accepted March 29, 2017.
- Copyright ©ERS 2017