Bicarbonate and functional CFTR channel are required for proper mucin secretion and link cystic fibrosis with its mucus phenotype

• Published in: The Journal of experimental medicine Vol. 209; no. 7; pp. 1263 - 1272
• Main Authors: Gustafsson, Jenny K, Ermund, Anna, Ambort, Daniel, Johansson, Malin E V, Nilsson, Harriet E, Thorell, Kaisa, Hebert, Hans, Sjövall, Henrik, Hansson, Gunnar C
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 02.07.2012
• Subjects: Animals; Basic Medicine; Bicarbonates; Bicarbonates - pharmacology; Cell and Molecular Biology; Cell- och molekylärbiologi; Confocal; Cystic Fibrosis; Cystic Fibrosis - genetics; Cystic Fibrosis - metabolism; Cystic Fibrosis - pathology; Cystic Fibrosis Transmembrane Conductance Regulator; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism; Dose-Response Relationship; Dose-Response Relationship, Drug; Drug; drug effects; Electron; Epithelium; Epithelium - drug effects; Epithelium - metabolism; Epithelium - pathology; Female; genetics; Ileum; Ileum - drug effects; Ileum - metabolism; Ileum - ultrastructure; Immunohistochemistry; In Vitro Techniques; Inbred C57BL; Intestinal Mucosa; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Intestinal Mucosa - ultrastructure; Intestine; Intestine, Small - drug effects; Intestine, Small - metabolism; Intestine, Small - pathology; Knockout; Male; Medicin och hälsovetenskap; Medicinska grundvetenskaper; metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy; Microscopy, Confocal; Microscopy, Electron, Transmission; Mucins; Mucins - secretion; Mucus; Mucus - drug effects; Mucus - metabolism; pathology; pharmacology; Phenotype; secretion; Small; Transmission; ultrastructure
• ISSN: 0022-1007; 1540-9538; 1540-9538
• DOI: 10.1084/jem.20120562

Cystic fibrosis (CF) is caused by a nonfunctional chloride and bicarbonate ion channel (CF transmembrane regulator [CFTR]), but the link to the phenomenon of stagnant mucus is not well understood. Mice lacking functional CFTR (CftrΔ508) have no lung phenotype but show similar ileal problems to humans. We show that the ileal mucosa in CF have a mucus that adhered to the epithelium, was denser, and was less penetrable than that of wild-type mice. The properties of the ileal mucus of CF mice were normalized by secretion into a high concentration sodium bicarbonate buffer (~100 mM). In addition, bicarbonate added to already formed CF mucus almost completely restored the mucus properties. This knowledge may provide novel therapeutic options for CF.