Abstract
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.
Funder
European Research Council
Vetenskapsrådet
Swedish Cancer Foundation
Knut och Alice Wallenbergs Stiftelse
IngaBritt och Arne Lundbergs Forskningsstiftelse
Sahlgrenska University Hospital
National Institute of Allergy and Infectious Diseases
The Swedish Foundation for Strategic Research
Erica Lederhausen’s Foundation
Lederhausen’s Center for CF Research at the University of Gothenburg
Cystic Fibrosis Foundation Therapeutics
Wilhelm and Martina Lundgren’s Foundation
The Swedish Heart and Lung Foundation
the Swedish Cystic Fibrosis Foundation
Magnus Bergvall´s Foundation
University of Gothenburg
Publisher
Springer Science and Business Media LLC