Cyclosporin A Binding to Calmodulin: A Possible Site of Action on T Lymphocytes
- 19 April 1985
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 228 (4697), 337-339
- https://doi.org/10.1126/science.3885394
Abstract
Cyclosporin A, a potent immunosuppressive agent, has been widely used to treat patients with solid organ transplants. Although its precise mechanism of action is unknown, it appears to inhibit subsets of T lymphocytes at an early stage in cell activation. Fluorescent, fully active derivatives of cyclosporin A and calmodulin, a protein that binds calcium and is therefore essential to normal cell function, were utilized to demonstrate that cyclosporin A binds to calmodulin. Flow cytometry showed that the calmodulin inhibitors R24571 and W-7 competitively inhibited binding of cyclosporin A to cloned T lymphocytes. Cyclosporin A inhibited the calmodulin-dependent activation of phosphodiesterase in a dose-dependent manner. Binding of cyclosporin A to calmodulin may prevent the latter's role in the activation of the second messengers and enzymes required for effective cell proliferation and function in the immune response.This publication has 17 references indexed in Scilit:
- Cyclophilin: A Specific Cytosolic Binding Protein for Cyclosporin AScience, 1984
- CYCLOSPORINE DOES NOT PREVENT CYTOPLASMIC CALCIUM CHANGES ASSOCIATED WITH LYMPHOCYTE ACTIVATIONTransplantation, 1984
- The role of calmodulin in the regulation of human lymphocyte activationCellular Immunology, 1984
- A fluorescent calmodulin that reports the binding of hydrophobic inhibitory ligandsBiochemical Journal, 1983
- Activation of T lymphocytes by 12-O-tetradecanoylphorbol-13-acetate is resistant to inhibition by cyclosporin AImmunology Letters, 1983
- Cyclosporin receptors on human lymphocytes.The Journal of Immunology, 1982
- Mechanism of T Cell Activation: Role and Functional Relationship of HLA‐DR Antigens and InterleukinsImmunological Reviews, 1982
- CalmodulinAdvances in protein chemistry, 1982
- Effect of cyclosporin A on human lymphocyte responses in vitro. II. Induction of specific alloantigen unresponsiveness mediated by a nylon wool adherent suppressor cell.The Journal of Immunology, 1981
- Cyclosporin A mediates immunosuppression of primary cytotoxic T cell responses by impairing the release of interleukin 1 and interleukin 2European Journal of Immunology, 1981