The Application of Bicarbonate Recovers the Chemical-Physical Properties of Airway Surface Liquid in Cystic Fibrosis Epithelia Models

SIMPLE SUMMARY: Cystic fibrosis (CF) is a multi-organ disease that affects the epithelia and exocrine glands, particularly the lungs, but also the pancreas, liver, kidneys, and intestines. Respiratory disease is the most common cause of death. Many of the problems in respiratory disease can be attributed to the viscous nature of the mucus. Indeed, thick mucus in the airways leads to reduced mucociliary clearance, chronic bacterial infections and inflammation followed by destruction of the lung parenchyma. The composition of the periciliary fluid (ASL) is regulated by the transport of water and ions through different ion channels and transporters distributed in a non-symmetrical way to the two parts of the epithelium. Mucus is the first line of defense against inhaled particles and protects the epithelium by trapping and eliminating harmful substances through the blink of the cells that push them towards the nose. In patients with CF the malfunction of the mutated CFTR causes a reduction in bicarbonate secretion with consequent reduction in the expansion of mucins and the formation of thick mucus. In this work we have shown that, in vitro, the administration of a solution containing bicarbonate ion would act not only on the osmotic component of the mucus, but directly on the expansion of the mucins by acting on its viscoelastic properties. ABSTRACT: Cystic fibrosis (CF) is a genetic disease associated with the defective function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein that causes obstructive disease and chronic bacterial infections in airway epithelia. Deletion of phenylalanine at position 508, p.F508del, the most frequent mutation among CF patients, causes a folding and traffic defect, resulting in a dramatic reduction in the CFTR expression. To investigate whether the direct application of bicarbonate could modify the properties of the airway surface liquid (ASL), we measured the micro-viscosity, fluid transport and pH of human bronchial epithelial cells monolayers. We have demonstrated that the treatment of a CF-epithelia with an iso-osmotic solution containing bicarbonate is capable of reducing both, the ASL viscosity and the apical fluid re-absorption. We suggest the possibility of design a supportive treatment based on topical application of bicarbonate, or any other alkaline buffer.