Proteome of airway surface liquid and mucus in newborn wildtype and cystic fibrosis piglets
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 befo...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12931-023-02381-x |
| _version_ | 1797863830050570240 |
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| author | Ana M. Rodriguez-Piñeiro Florian Jaudas Nikolai Klymiuk Andrea Bähr Gunnar C. Hansson Anna Ermund |
| author_facet | Ana M. Rodriguez-Piñeiro Florian Jaudas Nikolai Klymiuk Andrea Bähr Gunnar C. Hansson Anna Ermund |
| author_sort | Ana M. Rodriguez-Piñeiro |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T22:41:55Z |
| format | Article |
| id | doaj.art-bc91ee7d7b494a55acf02008062879a2 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-04-09T22:41:55Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-bc91ee7d7b494a55acf02008062879a22023-03-22T12:07:53ZengBMCRespiratory Research1465-993X2023-03-0124111210.1186/s12931-023-02381-xProteome of airway surface liquid and mucus in newborn wildtype and cystic fibrosis pigletsAna M. Rodriguez-Piñeiro0Florian Jaudas1Nikolai Klymiuk2Andrea Bähr3Gunnar C. Hansson4Anna Ermund5Department of Medical Biochemistry and Cell Biology, Sahlgrenska Academy, University of GothenburgCenter for Innovative Animal Models, Ludwig-Maximilians-UniversityCenter for Innovative Animal Models, Ludwig-Maximilians-UniversityCenter for Innovative Animal Models, Ludwig-Maximilians-UniversityDepartment of Medical Biochemistry and Cell Biology, Sahlgrenska Academy, University of GothenburgDepartment of Medical Biochemistry and Cell Biology, Sahlgrenska Academy, University of GothenburgAbstract 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.https://doi.org/10.1186/s12931-023-02381-xAcute phase proteinsAirway mucusCystic fibrosisMass-spectrometryMUC5BMUC5AC |
| spellingShingle | Ana M. Rodriguez-Piñeiro Florian Jaudas Nikolai Klymiuk Andrea Bähr Gunnar C. Hansson Anna Ermund Proteome of airway surface liquid and mucus in newborn wildtype and cystic fibrosis piglets Respiratory Research Acute phase proteins Airway mucus Cystic fibrosis Mass-spectrometry MUC5B MUC5AC |
| title | Proteome of airway surface liquid and mucus in newborn wildtype and cystic fibrosis piglets |
| title_full | Proteome of airway surface liquid and mucus in newborn wildtype and cystic fibrosis piglets |
| title_fullStr | Proteome of airway surface liquid and mucus in newborn wildtype and cystic fibrosis piglets |
| title_full_unstemmed | Proteome of airway surface liquid and mucus in newborn wildtype and cystic fibrosis piglets |
| title_short | Proteome of airway surface liquid and mucus in newborn wildtype and cystic fibrosis piglets |
| title_sort | proteome of airway surface liquid and mucus in newborn wildtype and cystic fibrosis piglets |
| topic | Acute phase proteins Airway mucus Cystic fibrosis Mass-spectrometry MUC5B MUC5AC |
| url | https://doi.org/10.1186/s12931-023-02381-x |
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