Proteome of airway surface liquid and mucus in newborn wildtype and cystic fibrosis piglets

Respiratory Research · 6 authors, 2 centres

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TL;DR

This study used mass-spectrometry proteomics on newborn piglet airway explants to compare the protein composition of washable surface liquid and attached mucus in wild-type and CFTR-null cystic fibrosis models. It found distinct protein clusters between these fractions and identified an additional acute phase protein cluster in CF piglets, suggesting an early inflammatory or developmental alteration at birth.

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The study analyzed unstimulated and carbachol-stimulated airway explants from newborn wild-type and cystic fibrosis (CF) piglets using mass-spectrometry based proteomics. The methods involved sequential collection of washable airway liquid fractions (1-4) and an Alcian blue-stained mucus fraction (5). Central results showed that proteins in fractions 1-4 clustered separately from the mucus fraction, which contained MUC5AC, MUC5B, and associated proteins like PDIs and lactoferrin. Carbachol stimulation increased MUC5AC and MUC5B levels. A distinct additional cluster of acute phase proteins, such as fetuin-A and fetuin-B, was observed in CF piglet washable fractions, indicating an early inflammatory response or altered lung development. Limitations include the use of a porcine model with indirect human relevance and the potential for some protein contamination from removed peripheral lung tissue. The findings imply CF airway disease is present at birth.

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other

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preclinical research

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ORIGINAL PAPER

PMC10022022

Proteome of airway surface liquid and mucus in newborn wildtype and cystic fibrosis piglets

Respiratory Research

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ABSTRACT

Background The respiratory tract is protected from inhaled particles and microbes by mucociliary clearance, mediated by the mucus and the cilia creating a flow to move the mucus cephalad. Submucosal glands secrete linear MUC5B mucin polymers and because they pass through the gland duct before reaching the airway surface, bundled strands of 1000–5000 parallel molecules exit the glands. In contrast, the surface goblet cells secrete both MUC5AC and MUC5B. Methods We used mass-spectrometry based proteomic analysis of unstimulated and carbachol stimulated newborn wild-type (WT) and cystic fibrosis transmembrane conductance regulator (CFTR) null (CF) piglet airways to study proteins in the airway surface liquid and mucus, to investigate if levels of MUC5AC and MUC5B were affected by carbachol stimulation and whether the proteins clustered according to function. Results Proteins in the first four extracted fractions clustered together and the fifth fraction contained the mucus cluster, mucins and other proteins known to associate with mucins, whereas the traditional airway surface liquid proteins clustered to fraction 1–4 and were absent from the mucus fraction. Carbachol stimulation resulted in increased MUC5AC and MUC5B. Conclusions These results indicate a distinct separation between proteins in the washable surface liquid and the mucus fraction. In fractions 1–4 from newborn CF piglets an additional cluster containing acute phase proteins was observed, suggesting an early inflammatory response in CF piglets. Alternatively, increased levels of these proteins could indicate altered lung development in the CF piglets. This observation suggests that CF airway disease is present at birth and thus, treatment should commence directly after diagnosis. Supplementary Information The online version contains supplementary material available at 10.1186/s12931-023-02381-x.

CITATION EXPORT

Ana M. Rodriguez-Piñeiro, Florian Jaudas, Nikolai Klymiuk et al.. Proteome of airway surface liquid and mucus in newborn wildtype and cystic fibrosis piglets. Respiratory Research. (2023). https://doi.org/10.1186/s12931-023-02381-x

AUTHORS

6 · 2 CENTRES

Ana M. Rodriguez-Piñeiro, Florian Jaudas, Nikolai Klymiuk, Andrea Bähr, Gunnar C. Hansson, Anna Ermund

1grid.8761.80000 0000 9919 9582Department of Medical Biochemistry and Cell Biology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
2grid.5252.00000 0004 1936 973XCenter for Innovative Animal Models, Ludwig-Maximilians-University, Munich, Germany