Alkyl-lysophospholipid induced suppression of human lymphocyte response to mitogens and selective killing of lymphoblasts

Abstract

Alkyl-analogs of 2-lysophosphatidylcholine have been found to inhibit the response of human peripheral blood lymphocytes to mitogens and allogeneic cells. Furthermore, these compounds kill selectively transformed lymphocytes in vitro while resting lymphocytes are not affected in their viability. The increased incorporation of fatty acids into cellular phospholipids during lymphocyte stimulation has been shown to be inhibited by these alkyl-lysophospholipids. Both resting and transformed lymphocytes could be shown to have an 1-0-alkyl-cleavage enzyme. Thus, selective cytotoxicity for lymphoblasts is not due to principal differences in the metabolism of alkyl-lysophospholipids as we have demonstrated to be the case between normal and leukemic cells, but is most likely due to the interference of these substances with the enhanced turnover of cellular phospholipids in stimulated lymphocytes.