Related Experiment Videos
Activation of CFTR chloride current by nitric oxide in human T lymphocytes
Y J Dong1, A C Chao, K Kouyama
1Department of Molecular Pharmacology and Medicine, Stanford University School of Medicine, CA 94305, USA.
Insights
Nitric oxide activates immune cell chloride currents via a cGMP pathway in healthy T cells. This pathway is impaired in cystic fibrosis, suggesting a potential immune defect in the disease.
Area of Science:
- Immunology
- Cellular Physiology
- Molecular Biology
Background:
- Nitric oxide (NO), produced by cytokine-activated mononuclear cells, is crucial for inflammation and immunity.
- While NO's cytotoxic role is known, its function as an immune cell signal transducer remains unclear.
Purpose of the Study:
- To investigate the role of nitric oxide as a signal transducer in human T cells.
- To explore the mechanism by which nitric oxide influences cellular function in T lymphocytes.
- To examine the potential link between nitric oxide signaling and cystic fibrosis.
Main Methods:
- Utilized whole-cell patch clamp recordings to measure ion channel activity.
- Studied nitric oxide-induced currents in normal human cloned T cells.
- Compared signaling pathways in normal T cells versus cystic fibrosis-derived T cells.
Main Results:
- Nitric oxide activates cystic fibrosis transmembrane conductance regulator (CFTR) chloride currents in normal human T cells.
- This activation occurs through a cyclic guanosine monophosphate (cGMP)-dependent mechanism.
- The identified nitric oxide signaling pathway is defective in T cells derived from cystic fibrosis patients.
Conclusions:
- Delineated a novel signal transduction mechanism for nitric oxide in immune cells.
- Findings suggest nitric oxide plays a previously unrecognized role in T cell function.
- Support the hypothesis of an intrinsic immune defect in cystic fibrosis.
Abstract:
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.