Cyclosporin A and FK506: molecular mechanisms of immunosuppression and probes for transplantation biology.
The microbial products cyclosporin A (CsA), FK506 and rapamycin are potent immunosuppressive agents. The introduction of CsA in the early 1970's significantly improved the outcome of organ and bone marrow allograft transplantation and advanced therapeutic options in autoimmune diseases. FK506 appears to have a higher therapeutic index than CsA, and has been used with encouraging results in clinical transplantation trials. FK506 and CsA, although structurally unrelated, appear to target similar signal transduction pathways in hematopoietic cells by inhibiting the action of calcineurin, a serine/threonine phosphatase. A structural analog of FK506, rapamycin, inhibits cellular function by a different molecular mechanism. These agents have advanced our understanding of signal transmission pathways in lymphocyte activation.
Bierer
B E
BE
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston.
Holländer
G
G
Fruman
D
D
Burakoff
S J
SJ
D000818:Animals; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000276:immunology; D016572:Cyclosporine / Q000276:immunology*; D006084:Graft Rejection / Q000517:prevention & control; D007108:Immune Tolerance / Q000276:immunology; D007165:Immunosuppression Therapy; D051379:Mice; D010749:Phosphoprotein Phosphatases / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D016559:Tacrolimus / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014181:Transplantation Immunology
D002148:Calmodulin-Binding Proteins; D016572:Cyclosporine; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D016559:Tacrolimus