ACTIVATION OF CFTR CHLORIDE CURRENT BY NITRIC-OXIDE IN HUMAN T-LYMPHOCYTES

Nitric oxide, which is produced by cytokine-activated mononuclear cells, is thought to play an important role in inflammation and immunity, While the function of nitric oxide as a direct cytotoxic effector molecule is well established, its function as a transducer molecule in immune cells is not, By use of whole-cell patch clamp recordings, we show that nitric oxide activates cystic fibrosis transmembrane conductance regulator Cl- currents in normal human cloned T cells by a cGMP-dependent mechanism, This pathway is defective in cystic fibrosis-derived human cloned T cells, These findings not only delineate a novel transduction mechanism for nitric oxide but also support the hypothesis that an intrinsic immune defect may exist in cystic fibrosis.