ACTIVATED LYMPHOCYTES INCREASE EXPRESSION OF 5-LIPOXYGENASE AND ITS ACTIVATING PROTEIN IN THP-1 CELLS

The aim of this study was to investigate the regulation of the 5-lipox ygenase pathway of arachidonic acid metabolism by lymphocytes using th e monocyte-like cell line, THP-1. When THP-1 cells were incubated over 4-7 days in 10% supernatant from lectin-activated human lymphocytes, their capacity to synthesize 5-lipoxygenase products was significantly increased. In contrast, the supernatant from nonactivated lymphocytes had no effect. The increase in capacity to synthesize 5-lipoxygenase products was mimicked by the addition of either granulocyte macrophage colony-stimulating factor (GM-CSF) or interleukin-3. These increases in synthetic capacity reflected increased enzymatic activity. Increase d immunoreactive protein and mRNA for the enzymes 5-lipoxygenase and 5 -lipoxygenase-activating protein were also found in cells conditioned with activated lymphocyte supernatants. Furthermore, the increase in m RNA for both enzymes was not blocked by cycloheximide, suggesting that the effect on steady-state mRNA levels does not require the synthesis of new protein. The increase in mRNA could be reproduced by GM-CSF. W e conclude that lymphocytes can regulate the expression of 5-lipoxygen ase in THP-1 cells over a period of days via the release of soluble fa ctors.