REGULATION OF PHOSPHOLIPID-METABOLISM BY K-CELL LINE - RELATIONSHIPS WITH CELL-PROLIFERATION AND INTERLEUKIN-2 PRODUCTION( CHANNEL BLOCKERSAND INHIBITORS OF CHOLINE TRANSPORT IN THE JURKAT T)

In the human T cell line Jurkat, three drugs generally used as effecto rs of K+ channels, i.e., quinine, 4-aminopyridine and tetraethylammoni um, modify phospholipid metabolism. The drugs inhibited the synthesis of both phosphatidylcholine and phosphatidylethanolamine. The mechanis m of such inhibition involves a decreased uptake of choline and ethano lamine by the cells, since the three K+ channel blockers were found to be able to competitively inhibit the high-affinity choline / ethanola mine transport system at the membrane level. In contrast, choline tran sport-inhibitors such as hemicholinium-3, decamethonium and dodecyltri methylammonium do not inhibit interleukin-2 synthesis and proliferatio n of the Jurkat T cell line. This indicates that the inhibition of eit her phosphatidylcholine and / or phosphatidylethanolamine synthesis is not directly implicated in these processes. The inhibition of interle ukin-2 synthesis appeared to be mediated through the inhibition ot dia cylglycerol production induced by T cell activators. A major role for phosphatidylserine in the regulation of T cell activation emerged, sin ce we demonstrated that a panel of K+ channel blockers enhanced the sy nthesis of this phospholipid mimicking the previously described effect of exogenously added phosphatidylserine in Jurkat cells, i.e., a bloc kade of interleukin-2 synthesis probably due to a defect in diacylglyc erol production.