Functional expression of the Na/K pump is controlled via a cyclosporin A-sensitive signalling pathway in activated human lymphocytes

An immunosuppressant cyclosporin A (CsA) inhibits T-cell proliferation by b locking the nuclear factor of activated T-cells (NFAT) required for express ion of the interleukin-2 (IL-2) gene. This work has demonstrated for the fi rst time that in human blood lymphocytes (HBLs) activated by phytohemagglut inin (PHA), CsA at anti-proliferative doses inhibits the late sustained inc rease in ouabain-sensitive Rb(K) influxes, which accompanies the growth pha se of G(0)/G(1)/S transition. CsA affects neither the initial, transient ac tivation of the pump in response to PHA nor the ouabain-resistant ion fluxe s during cell cycle progression. When the HBLs were rendered competent to p roliferate by phorbol 12,13-dibutyrate ester acid ionomycin in the presence of CsA, the exogenous IL-2 did not bypass the initial inhibitory effect of CsA on the long-term pump enhancement. When applied after the competence i nduction, CsA produced no effect on the sustained increase in ouabain-sensi tive Rb influxes during the IL-2-induced progression phase. These results i ndicate that in activated HBLs, (1) IL-2 is involved in functional expressi on of the Na/K pump during cell transition from quiescence to proliferation , (2) the cell cycle-associated upregulation of the pump is related to a Cs A-sensitive signalling pathway. (C) 1999 Federation of European Biochemical Societies.