In vitro metabolic inhibition of the human lymphocyte: influence on the expression of interleukin-2 receptors.

We have investigated the effects of energy depletion in human lymphocytes on the expression of the membrane-bound interleukin-2 receptor (IL-2R) and the release of soluble IL-2R. Concanavalin-A (Con-A) and IL-2-transformed lymphocytes were incubated with sodium fluoride, inhibiting the Embden-Meyerhof pathway, rotenone and 2,4-dinitrophenol (2,4-DNP), which are known to disturb mitochondrial high energy production. Rotenone was found to be the most potent inhibitor, with a half maximal effect at 10 nmol/L. 2,4-DNP and sodium fluoride, although not as potent as rotenone, showed marked inhibitory effects in higher concentrations, with half maximal effects at 50 mumol/L and 5 mmol/L respectively. No difference in the inhibition pattern for membrane-bound IL-2R compared with sIL-2R was observed. It is concluded that intracellular synthesis, transport and subsequent membrane insertion or release of receptors important for immunoregulation require high energy phosphate compounds and are sensitive to disturbances in intracellular energy levels.