Biochemical events associated with lymphocyte activation in aging. K+ transport and sensitivity of the Na+-K+ pump to digoxine.

The present investigation was directed toward answering the question of whether some age-related changes of membrane dependent triggering mechanisms during lymphocyte activation could account for the depressed T cell response to mitogens in aging. For this purpose, the K+ movements were analyzed in PHA-stimulated peripheral blood lymphocytes (PHA-PBL) from old humans (O) compared to adult (A). Indeed, plasma membrane Na+, K+, ATPase activation plays an essential role in cell proliferation and results from direct interaction between the loaded mitogen receptor and the enzyme. No difference could be found in the magnitude and the timing of the PHA-induced increase of K+ fluxes between PHA-PBL from O and A despite a higher K+ inflow in unstimulated but 20-hour preincubated PBL from O. Further experiments showed that the lectin-induced triggering mechanism of cation transport resulted from digoxine (DGX: a glycosid cardiotonic) sensitive ATPase. Moreover, whereas PBL from O exhibited a decreased PHA-induced DNA synthesis, DGX depressed the thymidine incorporation by 72-hour cultured PHA-PBL within the same inhibitory dose-related pattern in both O and A. We conclude that the triggering mechanism of Na+, K+-ATPase induced by PHA occurs adequately in early stimulated PBL from old subjects. In addition, digoxine sensitive structures work freely during PHA-induced lymphocyte proliferation in aging, thereby supporting further arguments for adequate Na+, K+-ATPase activity.