OMEGA-3-FATTY-ACID MODIFICATION OF MEMBRANE-STRUCTURE AND FUNCTION .2. ALTERATION BY DOCOSAHEXAENOIC ACID OF TUMOR-CELL SENSITIVITY TO IMMUNE CYTOLYSIS

Docosahexaenoic acid (DHA, 22:6) is a long-chain omega-3 fatty acid ab undant in cold water fish; it is the most unsaturated fatty acid found in biologic systems and is reported to alter membrane structure. To e xplore DHA's effect on membrane function, we have fused tumor cells wi th synthetic phosphatidylcholine (PC) containing stearic acid in the s n-1 position and DHA in the sn-2 position (18:0, 22:6 PC) and have fou nd the lipid-modified tumor cells to be more sensitive to cytolysis by alloreactive cytotoxic T lymphocytes. Cold target competition experim ents suggested that fusion of tumor plasma membranes with 18:0, 22:6 P C produced a qualitative change in expression of surface antigens reco gnized by cytotoxic T lymphocytes. We monitored the expression of vari ous epitopes on tumor cells by complement-mediated lysis and radioimmu noassay with monoclonal antibodies against H-2 class I antigens. Our r esults suggest that membrane-bound DHA increases the expression of som e epitopes while decreasing the expression of others and that differen t tumor lines vary in the magnitude of DHA's effect. Our findings are consistent with a model in which DHA-containing phospholipids segregat e into membrane domains, in turn altering the expression of membrane p roteins.