Calu-3: A human airway epithelial cell line that shows cAMP-dependent Cl^- secretion

Of 12 cell lines derived from human lung cancers, only Calu-3 cells showed high transepithelial resistance (R(te)) and increases in short-circuit current (I(sc)) in response to mediators. Calu-3 cells formed polarized monolayers with tight junctions and R(te) of ~100 Ω · cm². Baseline I(sc) was ~35 μA/cm² and was increased by ~75 μA/cm² on elevation of intracellular adenosine 3',5'-cyclic monophosphate (cAMP) by isoproterenol. Flux studies showed that the increase in I(sc) was due to Cl^- secretion. Forskolin and permeant analogues of cAMP also increased I(sc). Consistent with the presence of cAMP-dependent Cl^- secretion, immunoprecipitation demonstrated the presence of the cystic fibrosis transmembrane conductance regulator (CFTR). Bradykinin, methacholine, trypsin, and histamine all transiently (15-30 s) elevated I(sc), probably by increasing intracellular Ca concentration. Experiments in which the basolateral membrane was permeabilized with nystatin indicated that CFTR was substantially activated under baseline conditions and that Ca-activated Cl^- channels were absent from the apical membrane. We anticipate that Calu-3 cells will prove useful in the study of Cl^- secretion and other functions of human airway epithelial cells.