Back to Journals » International Journal of Chronic Obstructive Pulmonary Disease » Volume 10 » Issue 1

Protein networks in induced sputum from smokers and COPD patients

Authors Baraniuk JN, Casado B, Pannell LK, McGarvey PB, Boschetto P, Luisetti M, Iadarola P

Received 17 October 2014

Accepted for publication 1 April 2015

Published 15 September 2015 Volume 2015:10(1) Pages 1957—1975

DOI https://doi.org/10.2147/COPD.S75978

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Richard Russell

James N Baraniuk,1 Begona Casado,1 Lewis K Pannell,2 Peter B McGarvey,3 Piera Boschetto,4 Maurizio Luisetti,5,† Paolo Iadarola6

1Division of Rheumatology, Immunology and Allergy, Georgetown University, Washington, DC, 2Proteomics and Mass Spectrometry Laboratory, Mitchell Cancer Center, University of South Alabama, Mobile, AL, 3Innovation Center for Biomedical Informatics, Georgetown University, Washington, DC, USA; 4Department of Medical Sciences, University of Ferrara, Ferrara, 5SC Pneumologia, Dipartimento Medicina Molecolare, Fondazione IRCCS Policlinico San Matteo, 6Lazzaro Spallanzani Department of Biology and Biotechnology, University of Pavia, Pavia, Italy

Maurizio Luisetti passed away on October 20, 2014

Rationale: Subtypes of cigarette smoke-induced disease affect different lung structures and may have distinct pathophysiological mechanisms.
Objective: To determine if proteomic classification of the cellular and vascular origins of sputum proteins can characterize these mechanisms and phenotypes.
Subjects and methods: Individual sputum specimens from lifelong nonsmokers (n=7) and smokers with normal lung function (n=13), mucous hypersecretion with normal lung function (n=11), obstructed airflow without emphysema (n=15), and obstruction plus emphysema (n=10) were assessed with mass spectrometry. Data reduction, logarithmic transformation of spectral counts, and Cytoscape network-interaction analysis were performed. The original 203 proteins were reduced to the most informative 50. Sources were secretory dimeric IgA, submucosal gland serous and mucous cells, goblet and other epithelial cells, and vascular permeability.
Results: Epithelial proteins discriminated nonsmokers from smokers. Mucin 5AC was elevated in healthy smokers and chronic bronchitis, suggesting a continuum with the severity of hypersecretion determined by mechanisms of goblet-cell hyperplasia. Obstructed airflow was correlated with glandular proteins and lower levels of Ig joining chain compared to other groups. Emphysema subjects’ sputum was unique, with high plasma proteins and components of neutrophil extracellular traps, such as histones and defensins. In contrast, defensins were correlated with epithelial proteins in all other groups. Protein-network interactions were unique to each group.
Conclusion: The proteomes were interpreted as complex “biosignatures” that suggest distinct pathophysiological mechanisms for mucin 5AC hypersecretion, airflow obstruction, and inflammatory emphysema phenotypes. Proteomic phenotyping may improve genotyping studies by selecting more homogeneous study groups. Each phenotype may require its own mechanistically based diagnostic, risk-assessment, drug- and other treatment algorithms.

Keywords: cigarette smokers, chronic bronchitis, emphysema, proteomics, mucous hypersecretion, mucin 5AC, neutrophil extracellular nets

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Readers of this article also read:

Bacterial flora in the sputum and comorbidity in patients with acute exacerbations of COPD

Boixeda R, Almagro P, Díez-Manglano J, Cabrera FJ, Recio J, Martin-Garrido I, Soriano JB

International Journal of Chronic Obstructive Pulmonary Disease 2015, 10:2581-2591

Published Date: 1 December 2015

The stats are in: an update on statin use in COPD

Carlson AA, Smith EA, Reid DJ

International Journal of Chronic Obstructive Pulmonary Disease 2015, 10:2277-2284

Published Date: 22 October 2015

Does eosinophilic COPD exacerbation have a better patient outcome than non-eosinophilic in the intensive care unit?

Saltürk C, Karakurt Z, Adiguzel N, Kargin F, Sari R, Celik ME, Takir HB, Tuncay E, Sogukpinar O, Ciftaslan N, Mocin O, Gungor G, Oztas S

International Journal of Chronic Obstructive Pulmonary Disease 2015, 10:1837-1846

Published Date: 8 September 2015

Anticancer activities of self-assembled molecular bowls containing a phenanthrene-based donor and Ru(II) acceptors

Kim I, Song YH, Singh N, Jeong YJ, Kwon JE, Kim H, Cho YM, Kang SC, Chi KW

International Journal of Nanomedicine 2015, 10:143-153

Published Date: 25 August 2015

Magnetic removal of Entamoeba cysts from water using chitosan oligosaccharide-coated iron oxide nanoparticles

Shukla S, Arora V, Jadaun A, Kumar J, Singh N, Jain VK

International Journal of Nanomedicine 2015, 10:4901-4917

Published Date: 31 July 2015