CFTR and lysozyme secretion in human airway epithelial cells

Lysozyme is secreted in large quantities in human airways (10-20 mg/day), w here it helps to defend against bacterial and fungal infection. Lysozyme ex pression is restricted to the serous cells of the submucosal glands, which also express high levels of cystic fibrosis transmembrane conductance regul ator (CFTR) chloride channels. It is often assumed that mucus secretion in human airways is coupled to anion secretion through CFTR Cl- channels locat ed in the apical membrane. Therefore, a defect in CFTR function could cause abnormal mucus secretion leading to persistent bacterial infection and inf lammation of the airways. In this study we measured simultaneous secretion of lysozyme and Cl- from human airway epithelial serous cells. Secretion of lysozyme was measured by a turbidimetric assay that relies on the ability of lysozyme to disrupt the wall of the bacterium Micrococcus lysodeikticus, thus causing a fall in the optical density of the sample. Secretion of Cl- was measured as short-circuit current in a modified Ussing chamber. Activa tion of Cl- secretion by stimulation of cAMP- or Ca2+- dependent pathways c aused comparable increases in lysozyme secretion. Similarly, blockers of Cl - secretion, such as diphenylamine-2-carboxylate (DPC), also reduced lysozy me secretion. However, while treatment of airway submucosal gland cells wit h antisense oligonucleotides directed against CFTR reduced Cl- secretion, i t had no significant effect on the total amount of lysozyme secretion. Thes e results suggest a role for functional CFTR in regulation of lysozyme secr etion in human airways.