Differential effects of polyunsaturated fatty acids on cell growth and differentiation of premonocytic U937 cells

The effect of long chain polyunsaturated fatty acids (PUFA) on cell growth and differentiation was assessed in human premonocytic U937 cells. Addition of either 10 microM arachidonic acid (AA, 20:4n-6), eicosapentaenoic acid (EPA, 20:5n-3) or docosahexaenoic acid (DHA, 22:6n-3) resulted in the rapid incorporation of these fatty acids into cellular phospholipids. Their uptake was greatest in the first 2 h. AA and EPA reached steady-state levels after 8 h, while levels of DHA increased steadily over 72 h. In parallel, fatty acid metabolites derived from AA and EPA, 22:4n-6, 22:5n-6 and 22:5n-3, 22:6n-3, respectively, increased continuously indicating an active fatty acid elongation and desaturation. The effects of PUFA on monocytic differentiation were examined in cells which had been enriched with AA, EPA or DHA for 8 h and subsequently treated with retinoic acid (RA), 1,25-(OH)2-vitamin D3 (1,25-D3), interferon-gamma (IFN-gamma) or their combinations for 72 h. Growth of differentiating or non-differentiating U937 cells was not affected by enrichment with PUFA. However, in cells differentiated with 1,25-D3 plus IFN-gamma, prior enrichment with all three PUFA slightly but significantly (P < 0.05) increased the expression of the monocytic surface antigens CD11b and CD14 and generation of superoxide anion. The data indicate that although n-6 and n-3 PUFA are rapidly incorporated into phospholipids, they do not affect cell growth. However, enrichment with PUFA increases monocytic differentiation of U937 cells when induced most effectively with 1,25-D3 plus IFN-gamma.