An assessment of P-glycoprotein expression and activity in peripheral blood lymphocytes of transplant candidates.

BACKGROUND: P-glycoprotein (P-gp) is involved in the transport of the xenobiotic immunosuppressive agents and many cytokines, such as IL-2 and IFN-gamma. Hence, P-gp activity on peripheral blood lymphocytes (PBLs) could affect the pharmacologic response to xenobiotic immunosuppressants and immune responsiveness. The objectives of this study were to (1) determine the level of P-gp expression and activity on PBLs of kidney transplant candidates; and (2) determine whether P-gp expression correlates with P-gp activity.
METHODS: We measured P-gp expression and activity on CD3(+)/CD8(+), CD3(+)/CD4(+), B lymphocytes, and NK cells of 36 kidney transplant candidates using a flow cytometric assay. P-gp activity was determined for each subpopulation of cells by the ratio of the mean Rhodamine 123 fluorescence (MFI Rh123) in the presence of verapamil divided by the MFI Rh123 in the absence of verapamil. P-gp expression was noted as the percentage of P-gp(+) cells.
RESULTS: NK cells exhibited the greatest amount of P-gp activity (MFI Rh123 = 20.2 +/- 16.4) compared with other cell populations (P < .05). P-gp efflux activity was also significantly elevated in CD3(+)/CD8(+) cells (13.9 +/- 10.5) compared with B lymphocytes (4.9 +/- 2.7; P < .05) and CD4/CD3(+) cells (2.4 +/- 1.0; P < .05). P-gp expression was significantly higher in B lymphocytes (11.7 +/- 9.5) and NK cells (10.2 +/- 7.3) when compared with CD3(+)/CD8(+) cells (7.3 +/- 6.9) and CD3(+)/CD4(+) cells (6.4 +/- 3.8). P-gp expression was highly variable and did not correlate with P-gp activity (P > .05).
CONCLUSIONS: CD3(+)/CD8(+) cells and NK cells, exhibited significantly increased P-gp activity compared with the other cell populations. P-gp expression is not a good correlate of P-gp activity. These findings may have important implications for the use of immunosuppressive drugs posttransplant and immune responsiveness after transplantation.