[Inhibition of phosphatidylethanolamine and phosphatidylinositol synthesis, alteration of the G0 and G1 cell cycle phases and spontaneous apoptosis in lymphocytes from patients under immunosuppressive treatment].
Lymphocytes from patients treated with immunosuppressive agents were cultured for 48 hours either with or without concanavalin A. Phospholipid synthesis was then studied using 32p pulse-incorporation (5-hours pulses). Phosphatidylethanolamine synthesis was strongly decreased under immunosuppressive treatment: 1.5-fold in resting lymphocytes and 3- to 4-fold in concanavalin A-stimulated lymphocytes. Phosphatidylinositol synthesis also decreased about 2-fold in stimulated lymphocytes. These results indicate a loss of sensitivity of immunodeficient lymphocytes to the mitogen and an alteration of the G0 and the late G1 cell cycle phases. In parallel, but after a 72-hours incubation, lymphocytes were analysed by flow-cytofluorimetry with propidium iodide. Under concanavalin A-triggered stimulation, the entry into the S phase was much lower in immunodeficient lymphocytes as compared to standard. The characteristics of the G0-G1 population of lymphocytes were also modified. More importantly, after incubation in the culture medium in the absence of mitogen, we observed, among the immunodeficient lymphocytes, a high level of apoptotic cells, about 20 to 30%. This susceptibility to spontaneous apoptosis seems inherent to the status of immunodeficiency itself, whatever its origin. It may be related to the inhibition of phosphatidylethanolamine synthesis in the G0 phase.
Faculté de médecine Saint-Antoine, 27, rue Chaligny, 75012 Paris.
Claude
C
Rampini
Benoît
B
Barrou
Michel
M
Kornprobst
Jean-Claude
JC
Nicolas
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001379:Azathioprine / Q000494:pharmacology; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003208:Concanavalin A / Q000494:pharmacology; D003470:Culture Media / Q000494:pharmacology; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008563:Membrane Lipids / Q000096:biosynthesis*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000096:biosynthesis*; D010716:Phosphatidylinositols / Q000096:biosynthesis*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects* / Q000502:physiology; D016196:S Phase / Q000187:drug effects; D016559:Tacrolimus / Q000494:pharmacology
D003470:Culture Media; D007166:Immunosuppressive Agents; D008563:Membrane Lipids; D010714:Phosphatidylethanolamines; D010716:Phosphatidylinositols; D003208:Concanavalin A; D009173:Mycophenolic Acid; D001379:Azathioprine; D016559:Tacrolimus