Proteomic Changes of Alveolar Lining Fluid in Illnesses Associated with Exposure to Inhaled Non-Infectious Microbial Particles

Teirilä, Laura; Karvala, Kirsi; Ahonen, Niina; Riska, Henrik; Pietinalho, Anne; Tuominen, Päivi; Piirilä, Päivi; Puustinen, Anne; Wolff, Henrik

doi:10.1371/journal.pone.0102624

Cited by 3 publications

(1 citation statement)

References 80 publications

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“…Proteomic studies of BALF in healthy controls or patients with diverse pulmonary occupational alterations did not find proteins with protease activity in the BALF of normal individuals [ 13 ]. Most alveolar proteases are concentrated in granules or intracellularly in alveolar macrophages, and released under conditions of inflammation [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Metabolic Hormones, Apolipoproteins, Adipokines, and Cytokines in the Alveolar Lining Fluid of Healthy Adults: Compartmentalization and Physiological Correlates

Mendivil

Koziel

Brain³

2015

PLoS ONE

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ObjectivesOur current understanding of hormone regulation in lung parenchyma is quite limited. We aimed to quantify a diverse array of biologically relevant protein mediators in alveolar lining fluid (ALF), compared to serum concentrations, and explore factors associated with protein compartmentalization on either side of the air-blood barrier.Research Design and MethodsParticipants were 24 healthy adult non-smoker volunteers without respiratory symptoms or significant medical conditions, with normal lung exams and office spirometry. Cell-free bronchoalveolar lavage fluid and serum were analyzed for 24 proteins (including enteric and metabolic hormones, apolipoproteins, adipokines, and cytokines) using a highly sensitive multiplex ELISA. Measurements were normalized to ALF concentrations. The ALF:serum concentration ratios were examined in relation to measures of protein size, hydrophobicity, charge, and to participant clinical and spirometric values.ResultsALF measurements from 24 individuals detected 19 proteins, including adiponectin, adipsin, apoA-I, apoA-II, apoB, apoC-II, apoC-III, apoE, C-reactive protein, ghrelin, glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), glucagon, insulin, leptin, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, resistin, and visfatin. C-peptide and serpin E1 were not detected in ALF for any individual, and IL-6, IL-10, and TNF-alpha were not detected in either ALF or serum for any individual. In general, ALF levels were similar or lower in concentration for most proteins compared to serum. However, ghrelin, resistin, insulin, visfatin and GLP-1 had ALF concentrations significantly higher compared to serum. Importantly, elevated ALF:serum ratios of ghrelin, visfatin and resistin correlated with protein net charge and isoelectric point, but not with molecular weight or hydrophobicity.ConclusionsBiologically relevant enteric and metabolic hormones, apolipoproteins, adipokines, and cytokines can be detected in the ALF of healthy individuals. For the proteins measured, charge may influence trafficking and compartmentalization to the alveolar airspace more than molecular weight or hydrophobicity. These data may have implications for homeostasis and drug delivery to the lung.

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Section: Discussionmentioning

confidence: 99%

Metabolic Hormones, Apolipoproteins, Adipokines, and Cytokines in the Alveolar Lining Fluid of Healthy Adults: Compartmentalization and Physiological Correlates

Mendivil

Koziel

Brain³

2015

PLoS ONE

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Recent Trends in -Omics-Based Methods and Techniques for Lung Disease Prevention

Salhab

Pathak

2018

Genomics-Driven Healthcare

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Sarcoidosis Related Novel Candidate Genes Identified by Multi-Omics Integrative Analyses

Hočevar

Maver

Kunej

et al. 2018

OMICS: A Journal of Integrative Biology

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Sarcoidosis is a multifactorial systemic disease characterized by granulomatous inflammation and greatly impacting on global public health. The etiology and mechanisms of sarcoidosis are not fully understood. Recent high-throughput biological research has generated vast amounts of multi-omics big data on sarcoidosis, but their significance remains to be determined. We sought to identify novel candidate regions, and genes consistently altered in heterogeneous omics studies so as to reveal the underlying molecular mechanisms. We conducted a comprehensive integrative literature analysis on global data on sarcoidosis, including genomic, transcriptomic, proteomic, and phenomic studies. We performed positional integration analysis of 38 eligible datasets originating from 17 different biological layers. Using the integration interval length of 50 kb, we identified 54 regions reaching significance value p ≤ 0.0001 and 15 regions with significance value p ≤ 0.00001, when applying more stringent criteria. Secondary literature analysis of the top 20 regions, with the most significant accumulation of signals, revealed several novel candidate genes for which associations with sarcoidosis have not yet been established, but have considerable support for their involvement based on omic data. These new plausible candidate genes include NELFE, CFB, EGFL7, AGPAT2, FKBPL, NRC3, and NEU1. Furthermore, annotated data were prepared to enable custom visualization and browsing of these sarcoidosis related omics evidence in the University of California Santa Cruz (UCSC) Genome Browser. Further multi-omics approaches are called for sarcoidosis biomarkers and diagnostic and therapeutic innovation. Our approach for harnessing multi-omics data and the findings presented herein reflect important steps toward understanding the etiology and underlying pathological mechanisms of sarcoidosis.

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Proteomic Changes of Alveolar Lining Fluid in Illnesses Associated with Exposure to Inhaled Non-Infectious Microbial Particles

Cited by 3 publications

References 80 publications

Metabolic Hormones, Apolipoproteins, Adipokines, and Cytokines in the Alveolar Lining Fluid of Healthy Adults: Compartmentalization and Physiological Correlates

Metabolic Hormones, Apolipoproteins, Adipokines, and Cytokines in the Alveolar Lining Fluid of Healthy Adults: Compartmentalization and Physiological Correlates

Recent Trends in -Omics-Based Methods and Techniques for Lung Disease Prevention

Sarcoidosis Related Novel Candidate Genes Identified by Multi-Omics Integrative Analyses

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