Altered leukotriene B4 levels by HL-60 cells after monocytic/macrophage differentiation

The differentiation of HL-60 human promyelocytic leukaemia cells into specific monocytic or granulocytic lineage cells depending of the inductor agent is accompanied by selective regulation of several key enzymes involved in the synthesis of eicosanoids. In this communication we have investigated the changes in arachidonic acid metabolic profiles during phorbol 12-myristate 13-acetate (PMA)-induced monocytic differentiation of HL-60 cells. Our results show that HL-60 cells have spontaneous capacity to synthesize large amounts of LTB4, but PMA-differentiated cells lose the ability to release LTB4. Significant differences are found between HL-60 cells and PMA-treated cells in basal conditions and under ionophore stimulation. The addition of LTB4 at the time of PMA differentiation did not have effects on cell proliferation, but nordihydroguaiaretic acid (NDGA), a potent 5-lipoxygenase inhibitor, also inhibited HL-60 cell proliferation and did not have any effect on PMA-differentiated cell proliferation.