Amphotericin B restores host defenses in CF models

May 8, 2019 0 By FM

Muralgia et al demonstrated that an antifungal agent amphotericin B, which is capable of forming ion channels in the cellular membrane of airway epithelial cells, could restore ion transport and antibacterial defences in cystic fibrosis models. Cystic fibrosis is usually accompanied with abnormalities in the ion-channel protein CFTR which cause problems in the transport of chloride (Cl−) and bicarbonate (HCO3−) ions in the epithelial cells that line the airways of lungs, resulting in a build-up of mucous in these airways. The researchers tested amphotericin B in vitro human cells derived from CF patients and in pig models of the disease. When added to the apical membrane of human airway cells of the in vitro model, HCO3− was secreted from the cells which increased the pH of the airway-surface liquid which was then restored to a normal volume when compared to cell samples that did not receive amphotericin B. The researchers also tested the drug in airway epithelial cells obtained from people with cystic fibrosis caused by different mutations, including ones that did not yield CFTR, and observed enhancement of antibacterial activity and decreased viscosity of airway-surface liquid when compared to untreated cells. The findings reveal that the host defences in cystic fibrosis airway epithelia can be restored independent of CFTR via unselected small-molecule ion channels. Thus, the treatment proves to be effective independent of the genome causing the disease.

Source: Nature March 13,2019