title: Hyper-osmolarity and calcium chelation: Effects on cystic fibrosis mucus.
abstract: A non-functional Cystic Fibrosis Transmembrane conductance Regulator (CFTR) leads to the disease cystic fibrosis (CF). Although the CFTR is expressed in multiple organs, pulmonary disease is the major cause of illness and death in patients with CF. Stagnant mucus, causing airway obstruction, bacterial overgrowth, persistent inflammation and tissue destruction characterizes the disease, but how the defect in CFTR function is coupled to the mucus phenotype is still controversial. We have recently shown that bicarbonate ions passing through CFTR are necessary for proper unfolding of the MUC2 mucin, thus highlighting the importance of bicarbonate ion transport via the CFTR and the ability of these ions to raise the pH and chelate calcium bound to the mucin as the important steps in forming normal mucus. In order to find potential CF treatments and expand our knowledge about the usefulness of bicarbonate as an active ingredient in formulations to alleviate mucus plugging, we used an Ussing-type chamber and explants from the F508del-CFTR mutant mouse ileum to test the effect of calcium chelators on mucus attachment, either in isolation or in combination with osmolytes such as mannitol or hypertonic saline. We found that increasing the concentration of bicarbonate, both alone or in combination with increased osmolarity of the solution, detached the otherwise attached CF mucus.
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, Medicinaregatan 9A, SE-413 90 Gothenburg, Sweden. Electronic address: Anna.Ermund@medkem.gu.se.
authors.forename: Anna
authors.initials: A
authors.lastname: Ermund
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, Medicinaregatan 9A, SE-413 90 Gothenburg, Sweden.
authors.forename: Lauren N
authors.initials: LN
authors.lastname: Meiss
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, Medicinaregatan 9A, SE-413 90 Gothenburg, Sweden. Electronic address: Jenny.Gustafsson@medkem.gu.se.
authors.forename: Jenny K
authors.initials: JK
authors.lastname: Gustafsson
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, Medicinaregatan 9A, SE-413 90 Gothenburg, Sweden. Electronic address: Gunnar.Hansson@medkem.gu.se.
authors.forename: Gunnar C
authors.initials: GC
authors.lastname: Hansson
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D065096:Calcium Chelating Agents / Q000494:pharmacology*; D003550:Cystic Fibrosis / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D005260:Female; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009093:Mucus / Q000187:drug effects* / Q000378:metabolism*; D009154:Mutation; D009994:Osmolar Concentration
chemical_list: D001639:Bicarbonates; D065096:Calcium Chelating Agents; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: 2,2ʹ,2ʺ,2‴-(Ethane-1,2-diyldinitrilo)tetraacetic acid (PubChem CID: 6049); Calcium chelator; Carbachol (2-carbamoyloxyethyl(trimethyl)azanium; Erdosteine (PubChem CID: 65632); Hyperosmolarity; Mouse ileum; Mucus attachment; N-acetyl-l-cysteine (PubChem CID: 12035); Osmolyte; Prostaglandin E(2) (PubChem CID: 5280360); Sodium bicarbonate (PubChem CID: 767); chloride) (PubChem CID: 5831); d-mannitol (PubChem CID:6251)