Trans-stimulation of L-system amino acid transport in normal and chronic leukemic human lymphocytes: phorbol ester...

Chronic lymphocytic leukemia (CLL) B-lymphocytes have a unique and specific diminution of L-system (leucine favoring) amino acid uptake; the maximal velocity is approximately 10% of normal B-lymphocytes. Treatment of CLL B-cells with the maturational agent, tetradecanoyl phorbol acetate, results in restoration of L-system amino acid uptake to normal velocity. To further characterize the effect of phorbol ester on the L-system of CLL B-cells, we have examined the ability of normal and CLL lymphocytes to exchange intracellular for extracellular amino acids by the L-system (trans-stimulation). A 60% increase in L-system uptake was noted in normal B- and T-lymphocytes in the presence of a high intracellular concentration of 2-amino-2-carboxy-bicycloheptane (BCH), a largely L-system-specific substrate. L-system transport was not trans-stimulated in CLL B-lymphocytes. Phorbol ester treatment restored L-system uptake in CLL to a normal Vmax of 900 mumol/liter cell water per minute in the absence of BCH loading. The Vmax could be increased further to 2,400 if phorbol ester-treated CLL cells were loaded with BCH. Hence, phorbol esters result not only in a normalization of L-system uptake in CLL B-cells but the transport system demonstrates exchange rates comparable to normal lymphocytes.