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 CI- 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.
Dong
Y J
YJ
Department of Molecular Pharmacology and Medicine, Stanford University School of Medicine, CA 94305, USA.
Chao
A C
AC
Kouyama
K
K
Hsu
Y P
YP
Bocian
R C
RC
Moss
R B
RB
Gardner
P
P
D000634:Aminoquinolines / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018118:Chloride Channels / Q000502:physiology*; D002999:Clone Cells; D006152:Cyclic GMP / Q000502:physiology; D003550:Cystic Fibrosis / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D000634:Aminoquinolines; C505032:CFTR protein, human; D018118:Chloride Channels; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; C041715:6-anilino-5,8-quinolinedione; D001120:Arginine; D006162:Guanylate Cyclase; D010396:Penicillamine; D006152:Cyclic GMP