Measuring Mucociliary Transport and Mucus Properties in Multiple Regions of Airway Epithelial Surfaces Helps Clarify Cystic Fibrosis Defects

摘要

Cystic fibrosis (CF) lung disease occurs when mutations disable CF transmembrane conductance regulator (CFTR), an ion channel mediating Cl~- and HCO_3~- transport across epithelia. Unlike some gastrointestinal organs that are abnormal at birth, the lungs of humans and CF animal models appear to be healthy, although modest structural differences emerge under scrutiny (1). This near-normal appearance belies fundamental differences in ion transport that are seen in humans and animal models: CFTR-dependent, anion-mediated fluid secretion from surface epithelia and glands is reduced (2, 3). These transport defects cause CF mucus properties to differ: mucus is reduced in volume (3), has higher solids and viscosity (4), is more acidic (5), and is less able to kill bacteria (6). In addition, mucus clearance via ciliary action and cough, which may be the most important innate defense mechanism of the airways (7), also appears to be slowed. To repeat, all of these defects appear to arise from reduced anion-mediated fluid secretion, with reduced HCO_3~- secretion playing a critical role (8-10).