INHIBITION OF RECEPTOR-MEDIATED CALCIUM INFLUX IN T-CELLS BY UNSATURATED NONESTERIFIED FATTY-ACIDS

The effect of ω-3, ω-6 and ω-9 unsaturated fatty acids (UFAs) on receptor-mediated Ca2+ entry was investigated in a T-cell line (JURKAT) by using anti-CD3 antibodies (OKT3) to induce intracellular Ca2+ ([Ca2+](i)) increase and Ca2+ influx. All the UFAs, as well as Ni2+ ions and 12-O-tetradecanoylphorbol 13-acetate, decreased the OKT3-induced sustained [Ca2+](i) increase to basal levels. Although non-esterified fatty acids activate protein kinase C (PKC) [McPhail, Clayton and Snyderman (1984) Science 224, 622-624; Murakami, Chan and Routtenberg (1986) J. Biol. Chem. 261, 15424-15429], studies using H-7 and analysis of the PKC-dependent phosphorylation of 19 and 80 kDa marker substrates ruled out the involvement of PKC in UFA-induced inhibition of Ca2+ entry. Flow-cytometry analysis showed that UFAs do not interfere with antibody-receptor binding. BSA (0.2%, w/v) reversed the effect of UFAs after these fatty acids have decreased the OKT3-induced [Ca2+](i) increase to basal levels. The relevance of these findings and possible mechanisms for inhibition by UFAs of receptor-mediated Ca2+ influx were discussed.