HEMATOPOIETIC GROWTH-FACTOR INDUCTION OF GAMMA-GLUTAMYL TRANSFERASE IN THE KG-I MYELOID CELL-LINE

The enzyme gamma-glutamyl transferase (GGT) is a multifunctional enzym e that participates in a number of metabolic processes, including the conversion of leukotriene C4 (LTC4) to leukotriene D4 (LTD4). LTD4 is necessary for normal myeloid proliferation and differentiation. We hav e examined the ability of hematopoietic growth factors (HGF) to induce GGT enzyme activity and mRNA content in a HGF-responsive cell line (K G-1). Incubation of KG-1 with recombinant human cytokines interleukin- 1beta (IL-1beta), interleukin-3 (IL-3), granulocyte-macrophage colony- stimulating factor (GM-CSF), and tumor necrosis factor (TNF), but not interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF) or monocyte colony-stimulating factor (M-CSF), results in significant in creases in GGT enzyme activity. The increases in GGT activity are both dose- and time-dependent. In response to IL-1, increases in enzyme ac tivity are seen by 6 hours and activity is maximal by 24 hours. GGT mR NA increases also occur and peak by 3 to 6 hours. These results indica te that induction of increases in GGT mRNA levels and enzyme activity occur in myeloid cells in response to HGFs. This induction, together w ith the requirement for LTD4 for normal granulopoiesis, supports a rol e for GGT in the cellular events occurring in myeloid cells in respons e to HGFs.