Dataset Information

COPD lungs show an attached stratified mucus layer resembling the protective colonic mucus

ABSTRACT: Mucus accumulation is a key feature of respiratory diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). This is associated with goblet cell metaplasia and mucin overexpression, which can be induced by the increased activity of neutrophil elastase. The aim of the study was to characterization of mucus and epithelial cell proteomics in a porcine pancreatic elastase (PPE) mouse model of COPD/CF. The major proteins detected in mucus plugs obtained from PPE-treated mice included mucins Muc5ac and Muc5b, mucus-related proteins Clca1, Fcgbp, and Bpifb1. These proteins were upregulated in bronchoalveolar lavage (BAL) fluid and epithelial cells in mice exposed to elastase. Similar changes were found in BAL fluid of COPD patients.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Lung, Epithelial Cell

DISEASE(S): Chronic Obstructive Pulmonary Disease

SUBMITTER: Liisa Arike

LAB HEAD: Liisa Arike

PROVIDER: PXD006770 | Pride | 2018-10-22

REPOSITORIES: Pride

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Publications

Attached stratified mucus separates bacteria from the epithelial cells in COPD lungs.

Fernández-Blanco Joan Antoni JA Fakih Dalia D Arike Liisa L Rodríguez-Piñeiro Ana M AM Martínez-Abad Beatriz B Skansebo Elin E Jackson Sonya S Root James J Singh Dave D McCrae Christopher C Evans Christopher M CM Åstrand Annika A Ermund Anna A Hansson Gunnar C GC

JCI insight 20180906 17

The respiratory tract is normally kept essentially free of bacteria by cilia-mediated mucus transport, but in chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), bacteria and mucus accumulates instead. To address the mechanisms behind the mucus accumulation, the proteome of bronchoalveolar lavages from COPD patients and mucus collected in an elastase-induced mouse model of COPD was analyzed, revealing similarities with each other and with the protein content in colonic mucus. ...[more]

PMID: 30185674

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Project description:In this study we compared the intestinal mucus phenotype of Clca1-deficient (Clca1-/-) mice and wild-type (WT) controls. The human CLCA1 (chloride channel regulator, calcium-activated) and its murine ortholog mouse CLCA1 (formerly known as CLCA3) are secreted proteins which have been linked to human respiratory diseases such as asthma, cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) as well as to the corresponding murine models of these diseases. Common, disease severity-related features are goblet cell hyperplasia, mucus overproduction and disturbed clearance. Neutralization of mouse CLCA1 ameliorates the symptoms in the asthmatic mouse model and restoration of the decreased mouse CLCA1 protein level in a CF mouse model ameliorates the intestinal CF lesions, pointing toward these proteins being potential therapeutic targets. The expression CLCA1 can be induced in airways but this protein is normally expressed and secreted by goblet cells of the intestinal tract in both human and mouse together with the intestinal MUC2 mucin. This makes CLCA1 a major constituent of the extracellular intestinal mucus in which the MUC2 mucin is the main structural component. To study the possible further effects of murine CLCA1 deficiency on Muc2 and on other important components of the mucus, such as Agr2, Fcgbp, Klk and Zg16, a shotgun label-free proteomics study was performed which compared their relative abundance in the mucus layer, showing a tight and significant correlation between WT and Clca1-/- mucus proteins (Pearson r = 0.931, r2 = 0.868, p < 0.0001, based on 809 valid pairs). No significant differences in known mucus protein expression were observed. However, the abundance of CLCA1 in the mucus together with the domain structure suggests a structural role and other methods to reveal the function of these domains might shed light on the overall function in mucus. Because of its abundance in the mucus and the well preserved structure thought a long evolution together with mucus we still speculate that CLCA1 was developed to protect the expressing organism, although the threat is elusive.

Project description:Transcriptome profiling of E. coli MG1655, E. coli EDL933, E. coli ECOR26, and E. coli Nissle 1917 grown on mouse cecal mucus as carbon source The carbon sources that support growth of pathogenic E. coli O157:H7 in the mammalian intestine have not previously been investigated. In vivo, pathogenic E. coli EDL933 primarily grows as dispersed single cells within the mucus layer that overlies the mouse cecal epithelium. We therefore compared the pathogen and commensal E. coli MG1655 for their mode of metabolism in vitro on a mixture of the sugars known to be present in cecal mucus and found that the two strains used the thirteen sugars in a similar order and co-metabolized as many as nine sugars at a time. We conducted a systematic mutational analysis of E. coli EDL933 and E. coli MG1655 with lesions in the pathways used for catabolism of thirteen mucus-derived sugars and five other compounds for which the corresponding gene system was induced in the transcriptome of cells grown on cecal mucus. Each of 18 catabolic mutants in both genetic backgrounds was fed to streptomycin-treated mice together with the respective wildtype parent strain and their colonization was monitored in fecal plate counts. None of the mutations corresponding to the five compounds not found in mucosal polysaccharides resulted in colonization defects. Based on the mutations that caused colonization defects, we determined that both E. coli EDL933 and E. coli MG1655 used arabinose, fucose, and N-acetylglucosamine in the intestine. In addition, E. coli EDL933 used galactose, hexuronates, mannose and ribose, whereas E. coli MG1655 used gluconate and N-acetylneuraminic acid. The colonization defects of six catabolic lesions were found to be additive in E. coli EDL933, but not E. coli MG1655. The data indicate that pathogenic E. coli EDL933 uses sugars that are not used by commensal E. coli MG1655 to colonize the mouse intestine. The results suggest a strategy whereby invading pathogens gain advantage by simultaneously consuming several sugars that may be available because they are not consumed by the commensal intestinal microbiota. Keywords: growth condition: carbon source was mouse cecal mucus E. coli strains were grown on MOPS minimal medium containing 10 mg/ml of mucus or 0.2% glucose in 10 ml standing culture in testtubes and harvested at OD600 = 0.4.

Dataset Information

COPD lungs show an attached stratified mucus layer resembling the protective colonic mucus

Publications

Attached stratified mucus separates bacteria from the epithelial cells in COPD lungs.

Similar Datasets

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