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 |
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Authors: | Rampini Claude Barrou Benoît Kornprobst Michel Nicolas Jean-Claude |
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Affiliation: | Faculté de médecine Saint-Antoine, 27, rue Chaligny, 75012 Paris. |
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Abstract: | 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. |
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