Hypersensitivity to rapamycin of BJAB B lymphoblastoid cells.
Proliferation of the BJAB B-lymphoblastoid cell line was rapidly and almost completely suppressed by picomolar concentrations of the immunosuppressive macrolide rapamycin (50% inhibitory concentration 10-20 pM for cells reactivated from stationary phase). This cell line was considerably more sensitive to rapamycin than any other B-lymphoblastoid cell line tested, the Jurkat T-cell line or the HL60 promyelocytic cell line. BJAB cell proliferation was not affected by the related immunosuppressive macrolides FK506 or L-685,818, which bind to the immunophilin FKBP12 competitively with rapamycin and also inhibit its peptidylprolyl cis-trans isomerase activity. Excess FK506 or L-685,818 added simultaneously competitively antagonized rapamycin's anti-proliferative action. Levels of FKBP12 and uptake of rapamycin from the culture medium were also normal in BJAB cells. The hypersensitivity to rapamycin of BJAB cells thus reflects an unusual dependence on the intracellular signalling system targeted by the rapamycin-FKBP12 complex, and may provide a model system for elucidating the role played by this pathway in lymphocyte activation. The proliferation of BJAB cells reactivated from stationary phase can also be used as the basis for a highly sensitive bioassay for the presence of rapamycin in culture media or other biological fluids.
Kay
J E
JE
School of Biological Sciences, University of Sussex, Brighton, UK.
Smith
M C
MC
Frost
V
V
Morgan
G Y
GY
D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D011090:Polyenes / Q000494:pharmacology*; D020123:Sirolimus
D007166:Immunosuppressive Agents; D011090:Polyenes; D020123:Sirolimus