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. 2008 Jan 15;85(1):145-9.
doi: 10.1097/01.tp.0000296817.28053.7b.

Rapamycin, but not cyclosporine or FK506, alters natural killer cell function (VSports最新版本)

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Rapamycin, but not cyclosporine or FK506, alters natural killer cell function

Lu-En Wai et al. Transplantation. .

"VSports在线直播" Abstract

Infiltration of natural killer (NK) cells into solid organ allografts is observed in clinical and experimental transplantation. Studies suggest a role for NK cells in acute and chronic rejection of solid organ allografts; however, the effects of immunosuppressive agents on NK cells are not clearly established. Rat NK cell lines were analyzed for proliferation and cytotoxicity in the presence of cyclosporine, FK506, or rapamycin. Lewis recipients of DA liver allografts received immunosuppressive agents after transplantation VSports手机版. NK cells demonstrated robust function both in the absence and presence of cyclosporine and FK506. In contrast, rapamycin significantly inhibited proliferation and cytotoxicity of NK cells. NK cell numbers remained stable in graft recipients treated with cyclosporine and FK506, whereas there was a significant decrease in NK cells in rapamycin-treated recipients. These data indicate that immunosuppressive drugs have differential effects on NK cell function that may impact the immune response of transplant recipients. .

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VSports最新版本 - Figures

FIGURE 1
FIGURE 1
Effects of immunosuppressive agents on NK cell proliferation. RNK-16 cells (A) or primary rat NK cells (B) were incubated with CsA (0–100 ng/ml), FK506 (0–100 ng/ml), or rapamycin (0–10 ng/ml) for 24 hr (black bars) or 72 hr (gray bars). 3H-Tdr incorporation during an additional 18-hr incubation was measured. Values are the means±SEM of 3H-TdR incorporation (cpm)×103. The data shown is representative of three separate experiments. (C) RNK-16 cells were incubated with Rapa (0–10 ng/ml) for 24 hr. Cell cycle analysis was carried out by incubating cells for 30 min with propidium iodide solution before flow cytometric analysis. The percentage of apoptotic cells was determined as the percentage of cells in sub-G1 phase (left panel). Growth arrest was determined as the ratio of cells in G1 phase vs. the S and G2/M phases (right panel). The data shown is representative of two separate experiments.
FIGURE 2
FIGURE 2
Effects of immunosuppressive agents on NK cell function. (A) Primary NK cells were incubated with CsA, FK506, or rapamycin for 24 hr (diamonds) or 72 hr (squares) and supernatants analyzed for IFNγ levels. The data shown is representative of three separate experiments. (B) Primary NK cells were incubated alone (filled diamonds) or with CsA (open squares), FK506 (filled triangles) or Rapamycin (open circles) for 24 hr and then used as effectors in a killing assay against YAC-1 targets at E:T ratios of 8:1 to 1:1. P≤0.05 (NK cells alone vs. NK cells incubated with rapamycin). The data shown are representative of three separate experiments.
FIGURE 3
FIGURE 3
Rapamycin treatment decreases NK cell numbers posttransplantation. Lewis recipients of DA livers were treated with vehicle or CsA, FK506 and rapamycin for 7 days. (A) The proportion of NK cell levels in the peripheral blood on day 5 posttransplant. Data shown are the means ± SEM of three rats for each treatment. *P≤0.05 (vehicle treated graft recipients vs. graft recipients treated with Rapamycin as determined by Mann-Whitney U test). (B) The proportion of NK cell levels in the peripheral blood in control (diamonds) and rapamycin (circle) graft recipients. Data shown are the means ± SEM of three rats at each timepoint. *P<0.05 (vehicle treated graft recipients vs. graft recipients treated with Rapamycin as determined by Mann-Whitney U test).

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