Split-liver transplantation: One plus one doesn't always equal two
✍ Scribed by Robert M. Merion; Darrell A. Campbell Jr.
- Publisher
- John Wiley and Sons
- Year
- 1991
- Tongue
- English
- Weight
- 407 KB
- Volume
- 14
- Category
- Article
- ISSN
- 0270-9139
No coin nor oath required. For personal study only.
✦ Synopsis
tentatively identifying FKBP as a previously described 12 kD endogenous inhibitor of protein kinase C, raises the possibility that FK 506 exerts its effect by blocking activation of protein kinase C, a key step in antigeninduced T-cell activation. One possible model integrating this report with the work of Bierer et al. would be that FK 506 must bind to FKBP to elicit the protein kinase C inhibitory capacity of FKBP. FK 506 might activate FKBP by a conformational change or by directing FKBP to the proper subcellular compartment.
In either case, only the FK 506-FKBP complex is effective. Presumably, the rapamycin-FKBP complex acts in a different fashion or at a distinct intracellular site.
These studies highlight how much has been learned in recent years of the molecular events initiated by T-cell activation. They also underscore the complexity of the immune response and the risks of predicting drug effects based solely on chemical similarities. Furthermore, the difficulty in determining whether drugs with apparently distinct effects in vitro will be useful in combination should serve to emphasize that there is no substitute for rigorous in vivo testing. Ultimately, the goal of transplantation research is to induce a state of tolerance, or immunological unresponsiveness, to the graft. Although this remains an elusive goal, studies such as these advance us one step further by dissecting intracellular events that occur during the immune response. LAURENCE A.