PHOSPHATIDYLINOSITOL METABOLISM IN LYMPHOCYTES OF CHRONIC-ALCOHOLIC PATIENTS AFTER ANTI-CD3 STIMULATION

The immunological alterations observed in chronic alcoholic patients m ay be due to alterations of signal transduction across the lymphocyte membrane. Upon binding of mitogens or antigens to specific plasma memb rane receptors, the activation of phospholipase C leads to the hydroly sis of inositol phospholipids, producing inositol phosphates and diacy lglycerol. One of the early events in lymphocyte activation is an incr ease of intracellular calcium concentration, due to both an influx fro m extracellular fluid and a release from intracellular stores mediated by inositol phosphates. In this study we verified wether the diminish ed mobilization of intracellular calcium, previously observed in alcoh olics, is caused by alteration in phosphoinositide turnover. We evalua ted total inositol phosphate production in peripheral blood lymphocyte s after anti-CD3 stimulation, comparing control subjects and alcoholic patients. Lymphocyte activation generated inositol phosphates in both controls and alcoholics, but to a different extent, inositol phosphat e production being significantly higher in controls than in alcoholics . This reduction in inositol phosphate production could be accounted e ither to an inhibition of PLC activity or to a modified affinity of ph ospholipase C for its own substrates, i.e., phosphoinositides, which f atty acid composition has been previously demonstrated to be greatly d ifferent in alcoholics in comparison to healthy subjects.